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Τρίτη 28 Ιουνίου 2022

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

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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.

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Effect of Somatosensory Interaction Transcutaneous Electrical Acupoint Stimulation on Cancer-related Fatigue and Immunity: A Randomized Controlled Trial

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imageBackground: This study was intended to evaluate the clinical effect of somatosensory interaction transcutaneous electrical acupoint stimulation (SI-TEAS) on cancer-related fatigue (CRF) and its safety. Methods: The study protocol had been registered in China Clinical Trial Registration Center with registration number: ChiCTR2100045655. CRF patients were equally divided into SI-TEAS Group, Acupressure Group and Sham Acupressure Group to receive SI-TEAS, acupressure and sham acupressure treatments 5 times a week. The fatigue levels of patients in the 3 groups were measured by the Piper Fatigue Scale during the baseline period and after 4 and 8 weeks (of treatment). The cell immunity of these patients was determined by detecting the T-lymphocyte subsets and NK cells. Result: Of the 300 participants, 279 have gone through the independent rehabilitation intervention study, including 94 in the SI-TEAS Group, 92 in the Acupressure Group, and 93 in the Sham Acupressure Group. Intergroup comparisons of fatigue degree and cell immunity, namely SI-TEAS Group versus Acupressure Group, Acupressure Group versus Sham Acupressure Group, and SI-TEAS Group versus Sham Acupressure Group, showed that group changes observed during the baseline period and different time points after Week 4 and 8 were statistically different (P
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A Phase I Study of Apolizumab, an Anti-HLA-DR ß-chain Monoclonal Antibody, in Patients With Solid Tumor Malignancies

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imageBackground: Human leukocyte antigen (HLA)-DR, a member of the major histocompatibility complex class II antigen family, is a target for antibody-based therapeutics. Apolizumab (Hu1D10, Remitogen), a humanized IgG1 monoclonal anti-HLA-DR ß-chain antibody targets the antigen, 1D10, expressed on a wide variety of hematologic and solid tumor malignancies. In this Phase 1 trial, the maximum tolerated dose and dose-limiting toxicity of weekly apolizumab in patients with advanced solid tumor malignancies were determined. Patients and Methods: Eligible patients with refractory solid tumors were initially screened for ID10 Ag on their tumor. Patients whose tumors expressed 1D10 were administered apolizumab 0.5, 1.0, 1.5, or 3.0 mg/kg intravenously over 90 minutes weekly for 4 consecutive weeks, followed by a 4-week break, and assessment of response. Patients whose disease had not progressed were offered additional treatment. Results: Tumors from 75 patients were screened for 1D10 Ag of which 17 patients were positive and underwent treatment. The first 3 dose levels were well-tolerated. Dose-limiting toxicities of grade 3 infusion-related hypersensitivity reactions and grade 3 headache and hypertension occurred in 2 patients, respectively, at apolizumab 3.0 mg/kg. Four patients, 1 each with breast carcinoma, melanoma, renal cell carcinoma, and sarcoma had stable disease for a median of 15 weeks (range: 12 to 19 wk). Conclusion: Apolizumab can be administered safely at a maximum tolerated dose of 1.5 mg/kg for 4 consecutive weeks. Adverse events and limited clinical data in both hematologic and solid tumor malignancies resulted in discontinuation of clinical development of apolizumab. HLA-DR remains an interesting immunotherapeutic target.
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An Exploratory Study of Neoadjuvant Cetuximab Followed by Cetuximab and Chemoradiotherapy in Women With Newly Diagnosed Locally Advanced Cervical Cancer

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imageObjectives: 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.
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Sacituzumab Govitecan-hziy in Breast Cancer

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imageTrophoblast 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.
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Brain metastases: A Society for Neuro-Oncology (SNO) consensus review on current management and future directions

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Abstract
Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain metastases than cancer-related entities of similar incidence. Advances in oncologic care have heightened the importance of intracranial management. Here, in this consensus review supported by the Society for Neuro-Oncology (SNO), we review the landscape of brain metastases with particular attention to management approaches and ongoing efforts with potential to shape future paradigms of care. Each coauthor carried an area of expertise within the field of brain metastases and initially composed, edited, or reviewed their specific subsection of interest. After each subsection was accordingly written, multiple drafts of the manuscript were circulated to the entire list of authors for group discussion and feedback. The hope is that the these consensus guidelines will accelerate progress in the understanding and management of patients with brain metastases, and highlight key areas in need of further exploration that will lead to dedicated trials and other research investigations designed to advance the field.
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Blood T-cell profiling in metastatic melanoma patients as a marker for response to immune checkpoint inhibitors combined with radiotherapy

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Publication date: Available online 27 June 2022

Source: Radiotherapy and Oncology

Author(s): Gishan Ratnayake, Simone Reinwald, Jack Edwards, Nicholas Wong, Di Yu, Rachel Ward, Robin Smith, Andrew Haydon, Pei Au, Menno C. van Zelm, Sashendra Senthi

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

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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.

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Early treatment of high-risk hospitalized COVID-19 patients with a combination of interferon beta-1b and remdesivir: a phase 2 open-label randomized controlled trial

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Abstract
Background
Early antiviral therapy was effective in the treatment of COVID-19. We assessed the efficacy and safety of combined interferon beta-1b and remdesivir treatment in hospitalized COVID-19 patients.
Methods
We conducted a multicentre, prospective open-label, randomized-controlled trial involving high-risk adults hospitalized for COVID-19. Patients were randomly assigned to a 5-day interferon beta-1b 16 million units daily and remdesivir 200mg loa ding on day 1 followed by 100mg daily on day 2 to 5 (combination-group), or to remdesivir only of similar regimen (control-group) (1:1). The primary end-point was the time to complete alleviation of symptoms (NEWS2 = 0).
Results
Two-hundred and twelve patients were enrolled. The median days of starting treatment from symptom-onset was 3 days. The median age was 65 years and 159 patients (75%) had chronic disease. The baseline demographics were similar. There was no mortality. For the primary-endpoint, the combination-group was significantly quicker to NEWS2 = 0 (4 versus 6.5 days; hazard-ratio [HR],6.59; 95% confidence-interval [CI],6.1-7.09; p < 0.0001) when compared to the control-group. For the secondary endpoints, the combination-group was quicker to negative NPS VL (6 versus 8 days; HR,8.16; 95% CI,7.79-8.52; p < 0.0001) and develop seropositive IgG (8 versus 10 days; HR,10.78; 95% CI,9.98-11.58; p < 0.0001). All adverse events resolved upo n follow-up. Combination group (HR,4.1 95%CI,1.9-8.6, p < 0.0001), was the most significant independent factor associated with NEWS2 = 0 on day 4.
Conclusions
Early treatment with interferon beta-1b and remdesivir was safe and better than remdesivir only in alleviating symptoms, shorten viral shedding and hospitalization with earlier seropositivity in high-risk COVID-19 patients.
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Children's food choices are highly dependent on patterns of parenting practices and food availability at home in families at high risk for type 2 diabetes in Europe. Cross‐sectional results from the Feel4Diabetes‐study.

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ABSTRACT

Introduction

Food parenting practices, behaviours, and food availability at home are associated with children's food choices; however, these associations have been mainly studied for each parenting practice separately and focused mostly on healthy populations.

Aim

To identify patterns of parenting practices (including data regarding food availability at home, food and physical activity related behaviours and rewards) and to investigate their cross-sectional associations with children's food choices in families at high risk for type 2 diabetes (T2D).

Materials-Methods

Data of parents and children, (N=2278), from the Feel4Diabetes-study conducted in 6 European countries, were collected using validated questionnaires. The data analysed included children's food choices, food availability at home and food and physical activity related parenting practices. Four patterns of parenting practices were identified using principal component analysis and asso ciations between those components and children's food choices were assessed using adjusted, individual linear regressions.

Results

Parenting patterns focusing on unhealthy habits, such as allowing unhealthy snacks and unlimited screen time, providing higher availability of unhealthy foods at home, rewarding with snacks and screen time) were positively associated with children's unhealthy food choices (consumption of savoury/sweet snacks, fizzy drinks etc.). The parenting pattern providing fruit/vegetables availability at home, consuming fruit and being physically active with the child was positively associated with healthier children's food choices (consumption of fruit, vegetables, whole grain cereals etc.).

Conclusion

Public health initiatives should focus on families at high-risk for T2D, assisting them adopt appropriate parenting practices and behaviours to promote healthier food choices for children.

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