Despite advances in surgery and chemotherapy and the integration of antivascular endothelial growth factor therapy as well as poly(adenosine diphosphate–ribose) polymerase inhibitors into daily ...clinical practice, epithelial ovarian cancer remains the leading cause of death from gynecological cancer. The incorporation of new therapies with the potential to achieve long‐term disease remission is a clear need for patients with ovarian cancer. Immunotherapy with checkpoint inhibitors (CPIs) (antiprogrammed cell death protein 1 anti‐PD‐1 or antiprogrammed death‐ligand 1 anti‐PD‐L1) has been adopted in several malignancies based on improvements shown with regard to progression‐free survival and in particular overall survival. Although there is a solid rationale for the use of CPIs in patients with ovarian cancer, to our knowledge the clinical data presented to date are not very convincing. This article reviews the current data regarding CPIs in patients with ovarian cancer along with the future directions and designs of clinical trials aiming to overcome the low efficacy of CPIs in these individuals.
Clinical data regarding the use of checkpoint inhibitors (CPIs) as monotherapy have not been very convincing to date. The highest expectation currently is focused on the combination of CPIs with antiangiogenic agents and/or poly(adenosine diphosphate–ribose) polymerase inhibitors and the search for better biomarkers in the selection of patients.
Nanosystems with combined magnetic and plasmonic functionalities have in recent years become an active topic of research. By an adequate internal architecture of the constituting components, the ...magneto‐optical activity of these systems can be greatly increased due to the electromagnetic field enhancement associated with the plasmon resonance. Simultaneously, the magnetic functionality permits the control of the plasmonic properties by an external magnetic field, which allows the development of active plasmonic devices. These materials find applications in, for example, gas and biosensing areas, and in integrated photonic devices for telecommunications. In the present work the state of the art and current understanding of the phenomenology associated with magnetoplasmonic structures where magnetism and plasmonics are intertwined are reviewed.
Magnetoplasmonic systems possess both plasmonic and magnetic functionalities. By a smart combination of plasmonic and ferromagnetic materials with magnetooptical activity it is possible to design nanostructures whose magneto‐optical properties are enhanced by plasmon resonance excitation, and whose plasmonic properties are modulated by an external magnetic fi eld. These structures fi nd applications in sensing devices as well as in optical communications.
The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on ...endometrial cancer was held on 11-13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article.
A wide variety of marine mineral deposits were recovered from 750 to 1400 m water depths on Galicia Bank, Iberian margin. Mineral deposits include: (1) carbonate fluorapatite phosphorite slabs and ...nodules that replaced limestone and preserved original protolith fabric. (2) Ferromanganese vernadite crusts with high Mn and Fe (Mn/Fe = 1) contents, and thick stratabound layers consisting mainly of Mn (up to 27% MnO) and Fe (15% Fe2O3), which impregnated and replaced the phosphorite. (3) Co‐rich Mn nodules are composed of romanechite and todorokite laminae. Mn‐rich layers (up to 58% MnO) contain up to 1.8% Co. (4) Goethite nodules with Fe up to 67% Fe2O3 have low Mn and trace metals. We interpret this mineralization paragenesis to be related to major changes in oceanographic and tectonic regimes. Three phosphatization generations formed hardgrounds dated by 87Sr/86Sr isotopes as late Oligocene, early Miocene, and latest early Miocene. During the latest early Miocene, the hardground was fractured and breached due to regional intraplate tectonism, which was coeval with a widespread regional erosional unconformity. The stratabound layers and Co‐rich manganese nodules were derived from low‐temperature geothermally driven hydrothermal fluids, with fluid conduits along reactivated faults. During middle and late Miocene, the introduction of vigorous deep water flow from the Arctic generated growth of hydrogenetic ferromanganese crusts. Finally, growth of diagenetic Fe‐rich nodules (late Pliocene) was promoted by the introduction of hypersaline Mediterranean Outflow Water into the Atlantic Ocean.
Key Points:
Ferromanganese and phosphorite mineral deposits discovered on Galicia Bank
Paragenesis are controlled by hydrogenous, diagenetic, and hydrothermal processes
Cenozoic tectonism and paleoceanography are recorded on the mineralizations
The purpose of this study was to review the published evidence on the clinical use of nonsteroidal anti‐inflammatory drugs (NSAIDs) and to assess the cardiovascular risk (CVR) of cyclooxygenase‐2 ...inhibitors (coxibs), excluding aspirin, by means of a meta‐analytic procedure. A search was conducted on MEDLINE and EMBASE databases between October 1999 and June 2018. Cohort and case‐control studies showing CVR as relative risk (RR), odds ratio, hazard ratio, or incidence rate ratio associated with NSAIDs versus no treatment were selected. We estimated the pooled RR and the 95% confidence interval (CI) for all NSAIDs as a whole and individually. Eighty‐seven studies met the inclusion criteria. Overall, NSAIDs were found to be associated with a statistically significantly increased CVR (RR, 1.24 95%CI, 1.19‐1.28). The risk was slightly higher for coxibs (RR, 1.22 95%CI, 1.17‐1.28) as compared with nonselective NSAIDs (RR, 1.18 95%CI, 1.12‐1.24). Data analysis by drug disclosed that rofecoxib (RR, 1.39 95%CI, 1.31‐1.47), followed by diclofenac (RR, 1.34 95%CI, 1.26‐1.42) and etoricoxib (RR, 1.27 95%CI, 1.12‐1.43) were the NSAIDs associated with the highest CVR. Analysis by type of event showed that the highest risk corresponded to vascular events for both coxibs (RR, 2.18 95%CI, 1.72‐2.78) and nonselective NSAIDs (RR, 2.46 95%CI, 2.00‐3.02). The meta‐analysis results suggest that the use of the marketed coxibs celecoxib and etoricoxib would be related to a statistically significant CVR increase. Etoricoxib CVR could be higher than that for celecoxib. This increment would be similar to classical NSAID CVR.
The purpose of the study is to analyse and identify the stages of adoption of the blended learning (BL or b‐learning) methodology in higher education contexts, and to assess the relationship of these ...stages with a set of variables related to personal and professional characteristics, attributes perceived on BL and contextual variables. About 980 active academic staff from 43 Spanish public universities participated. The technology acceptance model (TAM) was used as a theoretical framework for the operational definition of the variables. Through the use of data mining techniques (clustering and decision trees), groupings were made based on the b‐learning adoption stage and a subsequent predictive model of these stages. The results show that the intention to use BL is the most important predictor variable in all models applied. In addition, the relationship between higher frequency of use and experience in digital educational environments with higher stages of implementation of the BL methodology was verified. Regarding the socio‐demographic variables included in the study, it was observed that they exert effects that are marginal in all cases.
Practitioner Notes
What is already known about this topic
Many universities and higher education institutions are designing strategic plans and diverse actions to implement and spread the use of BL methodologies.
TAM has been widely used to study the behaviour and the intention of using a wide variety of specific technologies in the classroom.
The study of BL from the perspective of TAM has generally been carried out using inferential analysis techniques.
What this paper adds
Analysis of complex systems such as the BL methodology from the TAM approach.
Groups of adopting teachers can be analysed using the TAM approach according to the stage of use of this innovation.
In contrast to traditional inferential techniques, this paper proposes a methodological procedure based on decision trees, which facilitates a more refined analysis of the relationship and interactions between the set of TAM predictor variables (PU, PEOU, BI, etc.) and the criterion variable (stages of adoption).
The obtaining of more complete and adjusted trees leads to better prediction and identification of the concrete actions that could be implemented by higher education institutions as protective or motivating factors for the diffusion of the BL methodology.
Implications for practice and/or policy
Interest in focusing attention on a complex system such as the one represented by the BL methodology from the perspective of models of technological acceptance reinforces an interesting line of research that can enrich the approach and scope of the TAM theory and generates knowledge that helps promote strategic actions to optimise the institutional diffusion of the BL training modality in higher education contexts.
Trastuzumab deruxtecan (T-DXd) is a human epidermal growth factor 2 (HER2)-directed antibody-drug conjugate approved in HER2-expressing breast and gastric cancers and HER2-mutant non-small-cell lung ...cancer. Treatments are limited for other HER2-expressing solid tumors.
This open-label phase II study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (immunohistochemistry IHC 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥1 systemic treatment or without alternative treatments. The primary end point was investigator-assessed confirmed objective response rate (ORR). Secondary end points included safety, duration of response, progression-free survival (PFS), and overall survival (OS).
At primary analysis, 267 patients received treatment across seven tumor cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. The median follow-up was 12.75 months. In all patients, the ORR was 37.1% (n = 99; 95% CI, 31.3 to 43.2), with responses in all cohorts; the median DOR was 11.3 months (95% CI, 9.6 to 17.8); the median PFS was 6.9 months (95% CI, 5.6 to 8.0); and the median OS was 13.4 months (95% CI, 11.9 to 15.5). In patients with central HER2 IHC 3+ expression (n = 75), the ORR was 61.3% (95% CI, 49.4 to 72.4), the median DOR was 22.1 months (95% CI, 9.6 to not reached), the median PFS was 11.9 months (95% CI, 8.2 to 13.0), and the median OS was 21.1 months (95% CI, 15.3 to 29.6). Grade ≥3 drug-related adverse events were observed in 40.8% of patients; 10.5% experienced adjudicated drug-related interstitial lung disease (ILD), with three deaths.
Our study demonstrates durable clinical benefit, meaningful survival outcomes, and safety consistent with the known profile (including ILD) in pretreated patients with HER2-expressing tumors receiving T-DXd. Greatest benefit was observed for the IHC 3+ population. These data support the potential role of T-DXd as a tumor-agnostic therapy for patients with HER2-expressing solid tumors.
•Two immunotherapies for recurrent/metastatic cervical cancer were approved in 2021.•Several trials are anticipated in recurrent/metastatic and locally advanced disease.•Some cases of ...difficult-to-treat adenocarcinoma or PD-L1-negative tumors responded.•Immunotherapy will become a new standard in the treatment of cervical cancer.
Cervical cancer constitutes a significant health burden for women globally. While most patients with early-stage disease can be cured with radical surgery or chemoradiotherapy, patients with high-risk locally advanced disease or with recurrent/metastatic disease have a poor prognosis with standard treatments. Immunotherapies are a rational treatment for this HPV-driven cancer that commonly expresses programmed cell death ligand-1. Before 2021, pembrolizumab was the only United States Food and Drug Administration-approved immunotherapy in cervical cancer, specifically for the second-line recurrent or metastatic (r/m) setting. In late 2021, the antibody-drug conjugate tisotumab vedotin was approved for second-line r/m cervical cancer and pembrolizumab combined with chemotherapy ± bevacizumab was approved for first-line r/m disease based on results from KEYNOTE-826. Moreover, with at least 2 dozen additional immunotherapy clinical trials in the second-line and first-line r/m setting, as well as in locally advanced disease, the treatment landscape for cervical cancer may eventually encounter a potential paradigm shift. Pivotal trials of immunotherapies for cervical cancer that were recently approved or with the potential for regulatory consideration through 2024 are reviewed. As immunotherapy has the opportunity to establish new standards of care in the treatment of cervical cancers, new biomarkers to identify the ideal patient populations for these therapies may also become important. However, issues with access, affordability, and compliance in low- and middle-income countries are anticipated.
Metal‐dielectric Au‐Co‐SiO2 magnetoplasmonic nanodisks are found to exhibit large magneto‐optical activity and low optical losses. The internal architecture of the nanodisks is such that, in resonant ...conditions, the electromagnetic field undertakes a particular spatial distribution. This makes it possible to maximize the electromagnetic field at the magneto‐optically active layers and minimize it in the other, optically lossy ones.
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