In this work, a comparison between the gate-driving requirements of p-GaN HEMTs with gate contact of Schottky and Ohmic type is presented. Furthermore, the presence of a gate current of different ...magnitude is experimentally verified for both types of devices. Successively, the possibility of using the gate current as a temperature-sensitive parameter and its monitoring during real circuit operation is proposed. The viability of monitoring the gate current without introducing additional complexity in the gate driver is examined through experimental measurements on commercially available p-GaN HEMTs.
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Background: Nivolumab and ipilimumab are associated with immune-related adverse events (irAEs) and, to date, few biomarkers predictive of ICIs toxicity are reported in mRCC. ...Methods: We conducted a single-center, observational, retrospective study at Clinical Oncology Unit, Careggi University Hospital, Florence, Italy. We evaluated 43 patients (pts) with mRCC treated with ICIs from April 2013 to May 2020. Absolute Eosinophil Counts (AEC, N°/μL) were registered at baseline and at time of occurrence of irAEs. This study aims to evaluate whether the AEC could be a predictive biomarker of irAEs in patients with mRCC treated with ICIs. Results: Median age was 65 years and males were 81.4%. 10 pts received Nivolumab+Ipilimumab, while 33 pts received Nivolumab single agent. 74.4% pts (32/43) developed at least 1 irAE, 11.6% with G3-G4 irAEs. The most frequent first irAE was endocrine event (40.6% pts; 37.5% with hypo-/hyper-thyroidism). The baseline mean AEC was 163.1/μL in our cohort, in particular 132.2/μL in pts who did not develop irAEs and 176.7/μL in pts who developed irAEs (p=0.134). Among the pts who developed irAEs, the mean AEC was lower in pts with G1-G2 (153.1/μL) than in those with G3-G4 (330/μL; p=0.0013) irAEs. At the time of onset of the first irAE, the mean AEC increased to 247/μL (Δ 140.1%). Analyzing the trend of AEC from baseline to time of occurrence of irAE for the 32 pts who had developed at least one irAE, 53.1% (17 pts) showed an increasing trend; among these pts, the most frequent irAEs were endocrine occurring in 4/17 pts (23.6%). An increasing trend was also observed in the majority of pts who developed G1-2 (14/27, 51.9%) and G3-4 (3/5, 60.0%) irAEs. Additional analyzes are ongoing to identify appropriate cut-offs of AEC to better stratify patients. Conclusions: There is little evidence in the literature about the potential role of absolute eosinophil counts as a predictive biomarker of irAEs in patients with solid tumors treated with ICIs, and most refer to patients with melanoma. In this study we observed that the baseline AEC values in patients that will develop irAEs are higher than in those without irAEs and, among the former, the values are lower for patients with toxicity G1-G2 vs G3-G4. We also found an increase of the mean AEC from baseline to the onset of the first irAE. Of the patients who experience toxicity, most have an upward trend in AEC at the onset of the first irAE. Compatibly with all the limitations of a retrospective analysis, our is the first experience exploring the role of the eosinophil count in the development of irAEs in mRCC patients treated with ICIs, and a prospective study is ongoing in our Unit to confirm the role of the eosinophil count in patients treated with ICIs.
Patients with metastatic colorectal cancer (mCRC) are routinely screened for either K- and N-RAS to select the appropriate treatment. The present study aimed to evaluate the concordance between K- ...and NRAS status in the tissue (either primary tumor or metastasis) and the plasma of patients with mCRC and to identify the associations between K- and NRAS mutations in ctDNA and the clinicopathological parameters. Samples from a total of 31 patients with mCRC with measurable disease according to the Response Evaluation Criteria in Solid Tumors were analyzed. For all patients, K- and NRAS status was determined in the tissue by matrix-assisted laser desorption/ionization time of flight mass spectrometry. For the detection of RAS mutations in cell-free tumor DNA also defined as circulating tumor DNA (ctDNA), the OncoBEAMR RAS CRC kit (Sysmex Inostics) was used. A total of 6/31 tissue samples expressed wild-type KRAS, whereas 25/31 presented mutations. In addition, 7/31 plasma samples expressed wild-type KRAS, mutations were detected in 22/31 patients, and for 2/31 patients, the test did not provide a conclusive result. A total of 24/31 patients expressed wild-type NRAS, 6/31 had mutations and 1/21 was not informative. For the KRAS mutational status, a moderate concordance (agreement, 85.18%; Cohen's k, 0.513) between the tissue and plasma analysis was observed; for NRAS, a fair agreement (agreement, 83.33%; Cohen's k, 0.242) was obtained. In conclusion, both tissue and plasma analyses should be performed for the management of patients with mCRC. To better exploit the beads, emulsions, amplification, magnetics (BEAMing) technique in the clinical setting, studies aimed at determining the RAS status to monitor therapy and during follow-up are warranted. Key words: metastatic colorectal cancer, KRAS, NRAS, mass spectrometry, beads, emulsions amplification, magnetics
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Background: Barriers for low recruitment in clinical trials have been classified based on three main sources: physician, patient, system. A primary role is played by a low ...patient awareness, which often leads to a lack of confidence in science and a substantial inability to estimate the benefits deriving from trial participation, aggravated by the spread of fake news. A prospective observational study was conducted to investigate the views of cancer patients on aspects of clinical research, their expectations, the level of comprehensibility of informed consent and the impact of the fake news phenomenon. Methods: From January 2018, after Ethics Committees approval, the ELPIS study was initiated in 9 Italian Medical Oncology Units. After signing the informed consent, patients were asked to complete a questionnaire, consisting of a set of multiple choice and Likert-score questions. Results: As of January 2021, 115 patients were enrolled, with a balanced sex distribution and a prevalence of subjects older than 55-years (79.8%). Regarding the previous knowledge about clinical research, the average score was 3.9 (range 1-5). The vast majority of respondents (91.3%) had already started experimental therapy and many of them constantly used internet (65.2%) and social networks (34.8%). More than half (53.9%) stated the interview with the physician was sufficient for a full understanding of informed consent. In case of doubt, the majority seeked support in the clinician (39.1%) while very few (1.7%) relied on the web. The average score attributed to doctor-patient relationship was equal to 8.89 (range 1-10). Respondents were quite confident in their ability to independently search for information on their disease, discriminate fake news and identify reliable sites (average score 3.26, 3.27, 3.09 respectively, over a range of 1-5). The scores related to the presumed ability to understand the results of a clinical study and to actively collaborate to produce research were high (average score 4.72 and 4.39 over a range of 1-5). Conclusions: Preliminary data from our research show a good level of patient awareness and a fine ability to understand information, discerning real from fake news. Continuing and implementing the training initiatives of the population in the health sector will certainly contribute to further improvement, hopefully obtaining an even greater involvement of patients in the early phases of research.
Interleukins (ILs) are involved in the occurrence and development of numerous types of cancer, and serve a critical role in the development of effective cancer therapeutics. The aim of the present ...study was to investigate the effect of IL-27 on chemotherapy resistance in lung cancer cells, and analyze its potential molecular mechanism in lung cancer tissues. Western blot analysis and reverse transcription-quantitative polymerase chain reaction were performed to examine the RNA and protein expression levels of IL-27. A Cell Counting Kit-8 assay was performed to evaluate the proliferation rates of the lung cancer line A549. Flow cytometry was subsequently applied to determine the rate of apoptosis in A549 cells. The data obtained revealed that the expression of IL-27 with cisplatin, significantly suppressed the proliferation and apoptosis of A549 cells compared with that in the cisplatin treatment group alone. The expression of Akt and apoptosis factors such as Caspase-3 and Bcl-2/Bax also ascertained that upregulated IL-27 inhibited the development of cancer and increased apoptosis in the A549 cells. Therefore, IL-27 may represent a potential target for antitumor therapy, especially when considering the clinical challenges presented by the development of chemoresistance in tumors. These findings suggest that IL-27 is a promising biomarker and represents a novel treatment strategy for patients with lung cancer.
Background: New trends are emerging in clinical research, such as patient empowerment and an active role in influencing health and research ethics. Patients' involvement is considered pivotal by ...stakeholders and institutions because they can channel the voice of those they represent, empowering their starring role in the different research activities.
Objectives: To obtain an overview of the real involvement of Italian patient associations in clinical research.
Methods: In January 2019, the Working Group 'Clinical Research Coordinators' of the Italian Association of Medical Oncology spread an online questionnaire consisting of 16 questions on the active involvement of patient associations in clinical research.
Results: The involvement in clinical research working groups, in the organization and implementation of specific activities and training initiatives is very limited (21.7% in both cases), as well as the active involvement in the conduct and/or definition of clinical trials (0.3%). Moreover, few associations (15.2%) have joined projects on patient involvement in clinical research in collaboration with other associations.
Discussion: Although the current involvement of the associations may have been somewhat underestimated, there is no doubt that much more can be done in terms of training and identification of common objectives between patients and professionals.
Background:
The Agenzia Italiana del Farmaco (AIFA) Determination 809/2015 sets all the requirements that clinical units and laboratories must meet in order to conduct phase I studies. Requirements ...include buildings, equipment, personnel, emergency management, as well as quality requirements defined in a set of standard operating procedures.
Methods:
In September 2018, the Italian Association of Medical Oncology working group, Clinical Research Coordinator, created an anonymous survey addressed to 51 medical directors of oncologic/hematologic clinical phase I units and all medical directors of generic and transversal units located in Italy and listed at the AIFA website.
Results:
Questionnaires from 24 institutions were collected, 9 previously inspected by competent authorities. All surveyed structures are certified to conduct profit studies and 1 is authorized to include healthy volunteers; 15 units implemented a Clinical Trial Quality Team in order to conduct nonprofit studies. At the time of data collection, a total of 398 proposals for phase I trials have been received, more than 50% coming from 3 institutes. A total of 144 phase I studies were active, with a median of 2.5 (Q1–Q3=0–6) studies for each center and asymmetric distribution of proposals.
Conclusion:
The considerable number of proposals received from the interviewed centers indicates that Italy plays an important role in the international pharmaceutical scene, despite bureaucratic procedures that threaten exclusion from decision-making. The AIFA Determination will be an important opportunity to acquire a competitive working approach.
Although contract research organization (CRO) support is commonly included in clinical trial management, its hypothetical effect in terms of time savings and benefit has never been quantified. Thus, ...we retrospectively analyzed 113 lung cancer trials to evaluate the activation timelines and patient accrual according to CRO involvement. The exploratory results of our analysis suggest that bureaucratic procedures might require more time in CRO-administered trials than in sponsor-administered and CRO-free studies, which also result in greater numbers of patient screening and enrollment.
Contract research organization (CRO) support is largely included in clinical trial management, although its effect in terms of time savings and benefit has not yet been quantified. We performed a retrospective multicenter analysis of lung cancer trials to explore differences in term of trial activation timelines and accrual for studies with and without CRO involvement.
Results regarding study timelines from feasibility data to first patient enrollment were collected from 7 Italian thoracic oncology departments. The final accruals (screened/enrolled patients) are reported. We considered CRO/sponsor-administered and CRO-free trials according to who was responsible for the management of the crucial setup phases.
Of 113 trials, 62 (54.9%) were CRO-administered, 34 (30.1%) were sponsor-administered, and 17 (15.0%) were CRO-free. The median time from feasibility invitation to documentation obtainment was 151 days in the CRO-administered trials versus 128 in the sponsor-administered and 120 in the CRO-free trials. The time from document submission to contract signature was 142 days in the CRO-administered versus 128 in the sponsor-administered and 132 in the CRO-free trials. The time from global accrual opening to first patient enrollment was 247 days for the CRO-administered versus 194 in the sponsor-administered and 151 in the CRO-free trials. No significant differences were observed in terms of the median overall timeline: 21 months in the CRO-administered, 15 in the sponsor-administered, and 18 months in the CRO-free studies (P = .29).
Although no statistically significant differences were identified, the results of our analysis support the idea that bureaucratic procedures might require more time in CRO-administered trials than in sponsor-administered and CRO-free studies. This bureaucratic delay could negatively affect Italian patients’ screening and enrollment compared with other countries.
L'A. mette in rilievo l'incertezza delle nostre conoscenze sulla questione della proporzione dei sessi nelle nascite. Taie incertezza è conseguenza della scarsezza del materiale statistico, il quale ...non permette di individuare la complessa azione di quelle circostanze che mascherano l'effetto delle cause determinanti la suddetta proporzione. L'A. met en relief l'incertitude de nos connaissances sur la question de la proportion des sexes dans les naissances. Cette incertitude est la conséquence du défaut de matériel statistique, qui ne permet pas d'invidualiser l'action complexe des circonstances qui cachent les effets des causes qui déterminent la proportion sus dite. Der Vf. zeigt, wie unbefriedigend noch immer unsere Kenntnisse in der Frage nach der Proportion der Knaben-und Mädchengeburten sind. Den Grund sieht er in der Mangelhaftigkeit unseres statistischen Materials, welches uns nicht erlaubt, die die Auswirkung der geschlechtsbestimmenden Ursachen charakterisierenden Faktoren ihrem ganzen Umfange nach zu würdigen. The A. points out the uncertainty of our knowledge ou the question of the proportion of sexes in birth. Such an uncertainty is a consequence of the scarcity of statistical material, which does not allow us to make out the complex action of those circumstances that hide the effect of the causes which determine the above mentioned proportion.
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