The diagnostic and prognostic value of serum exosome‐derived carbamoyl phosphate synthase 1 in HEV‐related acute liver failure patients

alexandrossfakianakis shared this article with you from Inoreader The diagnostic and prognostic value of serum exosome‐derived carbamoyl phosphate synthase 1 in HEV‐related acute liver failure patients via Journal of Medical Virology Abstract Background Early diagnosis and prognosis evaluation are of great significance to HEV-related acute liver failure (HEV-ALF) patients Methods We collected serum samples from 200 health controls (HCs), 200 patients with acute hepatitis E (AHE) and 200 HEV-ALF patients to evaluate serum exosome-derived carbamoyl phosphate synthase 1 (CPS1) levels and determine its diagnostic and prognostic value. Results The exosome-derived CPS1 levels in the HEV-ALF group were significantly higher than those in the AHE and HCs groups. The AUC of exosome-derived CPS1 to predict the occurrence of HEV-ALF was 0.850 (0.811-0.883). Both logistical regression and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that exosome-derived CPS1 is independent risk factor for HEV-ALF. The exosome-derived CPS1 levels were positively correlated with organ failure, and the outcomes in HEV-ALF patients. The exosome-derived CPS1 levels in the worsening group wer e significantly higher than those in the fluctuating and the improving groups. The AUC of serum exosome-derived CPS1 to predict 30-day mortality was 0.829 (0.770-0.879), which was significantly greater than that of the Child-Pugh, KCH, and MELD model. Conclusions The level of serum exosome-derived CPS1 might serve as promising diagnostic and prognostic biomarker for HEV-ALF patients, which may provide better guidance for the diagnosis, prognosis and treatment of HEV-ALF patients. This article is protected by copyright. All rights reserved. View on Web

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An Exploratory Study of Neoadjuvant Cetuximab Followed by Cetuximab and Chemoradiotherapy in Women With Newly Diagnosed Locally Advanced Cervical Cancer

alexandrossfakianakis shared this article with you from Inoreader An Exploratory Study of Neoadjuvant Cetuximab Followed by Cetuximab and Chemoradiotherapy in Women With Newly Diagnosed Locally Advanced Cervical Cancer via American Journal of Clinical Oncology - Current Issue Objectives: This study explored the feasibility of cetuximab with chemoradiation in women with cervical carcinoma and evaluated fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) to assess early response to cetuximab (NCT00292955). Patients and Methods: Eligible patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVB invasive carcinoma of the uterine cervix were treated on 1 of 3 dose levels (DL). DL1 consisted of neoadjuvant cetuximab, then concurrent radiotherapy with cetuximab 250 mg/m2/cisplatin 40 mg/m2, followed by weekly cetuximab. DL2 consisted of radiotherapy with cetuximab 200 mg/m2 and cisplatin 30 mg/m2. DL3 consisted of radiotherapy with cetuximab 250 mg/m2 and cisplatin 30 mg/m2. Patients underwent 18F-FDG-PET/CT before treatment, after neoadjuvant cetuximab, and at the end of treatment. Results: Of the 21 patients enrolled, 9, 3, and 9 were treated in DL1, DL2, and DL3, respectively. DL1 required dose reductions due to gastrointestinal toxicities. DL2 and 3 were tolerated with 1 dose-limiting toxicity (grade 4 renal failure) at DL3. Following 3 weekly treatments of neoadjuvant cetuximab in DL1, 7 patients had maximum standardized uptake value changes on 18F-FDG-PET/CT consistent with response to cetuximab. Of the 12 patients with locally advanced disease, eleven evaluable patients had no evidence of disease on 18F-FDG-PET/CT at treatment end. Five-year progression-free survival and overall survival rates for all patients were 57.5% and 58.5%, respectively. Conclusions: Cetuximab with cisplatin 30 mg/m2 and radiotherapy was tolerated. 18F-FDG-PET/CT demonstrated early evidence of response to neoadjuvant cetuximab. With advances in precision oncology and the recent approval of pembrolizumab in metastatic cervical cancer, dual-target inhibition with an epidermal growth factor receptor inhibitor may be a promising treatment in the future. View on Web

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Sacituzumab Govitecan-hziy in Breast Cancer

alexandrossfakianakis shared this article with you from Inoreader Sacituzumab Govitecan-hziy in Breast Cancer via American Journal of Clinical Oncology - Current Issue Trophoblast cell-surface antigen-2 (Trop-2) is a transmembrane calcium signal transducer and its overexpression is common in many types of malignant epithelial tumors, including breast cancer (BC). Sacituzumab govitecan-hziy (SG), the anti-Trop-2 antibody-drug conjugate, resulted in a significant survival benefit over chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). The greatest efficacy was observed in those who had a medium or high Trop-2 score. However, the importance of Trop-2 as a potential predictive factor requires further research. Elderly patients also appear to b enefit from treating with SG. While the early results are encouraging, the ultimate benefit of SG in patients with brain metastases has yet to be determined. Early phase studies have shown that SG is also active in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic BC. The most common side effects of SG are nausea, neutropenia and diarrhea. Currently, several clinical trials are in progress with SG in monotherapy and in combination treatment for various types of BC. Taken together, SG should be considered as a new standard of care in patients with pretreated mTNBC. This review summarizes the development and highlights recent advances of the SG in BC. View on Web

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Irrigant flow in the root canal during ultrasonic activation: a numerical fluid‐structure interaction model and its validation

alexandrossfakianakis shared this article with you from Inoreader Irrigant flow in the root canal during ultrasonic activation: a numerical fluid‐structure interaction model and its validation via International Endodontic Journal Abstract Aim a. To develop a three-dimensional numerical model combining the oscillation of a tapered ultrasonic file and the induced irrigant flow along with their two-way interaction in the confinement of a root canal. b. To validate this model through comparison with experiments and theoretical (analytical) solutions of the flow. Methodology Two partial numerical models, one for the oscillation of the ultrasonic file and another one for the irrigant flow inside the root canal around the file, were created and coupled in order to take into account the two-way coupled fluid-structure interaction. Simulations were carried out for ultrasonic K-files and for smooth wires driven at four different amplitudes in air or inside an irrigant-filled straight root canal. The oscillation pattern of the K-files was determined experimentally by Scanning Laser Vibrometry and the flow pattern inside an artificial root canal was analyzed using high-speed imaging together with Particle Image Velocimetry. Analytical solutions were obtained from an earlier study. Numerical, experimental and analytical results were compared to assess the validity of the model. Results Comparison of the oscillation amplitude and node location of the ultrasonic files and of the irrigant flow field showed a close agreement between the simulations, the experiments, and the theoretical solutions. Conclusions The model is able to predict reliably the file oscillation and irrigant flow inside root canals during ultrasonic activation under similar conditions. View on Web

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