Cabozantinib for the treatment of solid tumors: a systematic review

Cabozantinib; Hepatocellular carcinoma; Solid tumorCabozantinib; Carcinoma hepatocel·lular; Tumor sòlidCabozantinib; Carcinoma hepatocelular; Tumor sólidoBackground: Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been investigated for the treatment of other cancers. With the available evidence and the real-world performance of cabozantinib compared with clinical trial data, we performed a systematic review of cabozantinib monotherapy as treatment for solid tumors in adults. Methods: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with PROSPERO (CRD42020144680). We searched for clinical and observational studies of cabozantinib monotherapy for solid tumors using Embase, MEDLINE, and Cochrane databases (October 2020), and screened relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Small studies (n < 25) and studies of cabozantinib combination therapies were excluded. Quality was assessed using National Institute for Health and Care Excellence methodology, and study characteristics were described qualitatively. Results: Of 2888 citations, 114 were included (52 randomized studies, 29 observational studies, 32 nonrandomized phase I or II studies or pilot trials, and 1 analysis of data from a randomized study and a nonrandomized study). Beyond approved indications, other tumors studied were castration-resistant prostate cancer, urothelial carcinoma, Ewing sarcoma, osteosarcoma, uveal melanoma, non-small-cell lung cancer, Merkel cell carcinoma, glioblastoma, pheochromocytomas and paragangliomas, cholangiocarcinoma, gastrointestinal stromal tumor, colorectal cancer, salivary gland cancer, carcinoid and pancreatic neuroendocrine tumors, and breast, endometrial and ovarian cancers. The most common adverse events were hypertension, diarrhea, and fatigue. Conclusion: The identified evidence demonstrates the positive efficacy/effectiveness of cabozantinib monotherapy in various solid tumor types, with safety findings being consistent with those observed with other VEGFR-targeting tyrosine kinase inhibitors. When available, real-world findings were consistent with the data reported from clinical trials. A limitation of this review is the high proportion of abstracts; however, this allowed us to capture the most up-to-date findings.The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by Ipsen

Transcatheter Edge-to-Edge Treatment of Functional Tricuspid Regurgitation in an Ex Vivo Pulsatile Heart Model

Although associated with left heart pathologies, functional tricuspid regurgitation (FTR) is often left untreated during left heart surgery. Hence, owing to its degenerative character, reoperation is often needed, encompassing an impressive (25% to 35%) mortality rate. Thus transcatheter approaches to FTR are raising great interest

Li in NGC 6752 and the formation of globular clusters

Li abundances for 9 Turnoff (TO) stars of the intermediate metallicity cluster ([Fe/H]=-1.4) NGC6752 are presented. The cluster is known to show abundance anomalies and anticorrelations observed in both evolved and main sequence stars. We find that Li abundance anticorrelates with Na (and N) and correlates with O in these Turn-Off stars. For the first time we observe Pop II hot dwarfs systematically departing from the Spite plateau. The observed anticorrelations are in qualitative agreement with what is expected if the original gas were contaminated by Intermediate Mass AGB - processed material. However, a quantitative comparison shows that none of the existing models can reproduce all the observations at once. The very large amount of processed gas present in the cluster does not imply a 'pollution', but rather that the whole protocluster cloud was enriched by a previous generation of stars. We finally note that the different abundance patterns in NGC 6397 and NGC 6752 imply different ejecta of the preenrichment composition for the two clusters.Comment: Accepted for publication on A&

POISSON project - II - A multi-wavelength spectroscopic and photometric survey of young protostars in L 1641

Characterising stellar and circumstellar properties of embedded young stellar objects (YSOs) is mandatory for understanding the early stages of the stellar evolution. This task requires the combination of both spectroscopy and photometry, covering the widest possible wavelength range, to disentangle the various protostellar components and activities. As part of the POISSON project, we present a multi-wavelength spectroscopic and photometric investigation of embedded YSOs in L1641, aimed to derive the stellar parameters and evolutionary stages and to infer their accretion properties. Our database includes low-resolution optical-IR spectra from the NTT and Spitzer (0.6-40 um) and photometric data covering a spectral range from 0.4 to 1100 um, which allow us to construct the YSOs spectral energy distributions (SEDs) and to infer the main stellar parameters. The SED analysis allows us to group our 27 YSOs into nine Class I, eleven Flat, and seven Class II objects. However, on the basis of the derived stellar properties, only six Class I YSOs have an age of ~10^5 yr, while the others are older 5x10^5-10^6 yr), and, among the Flat sources, three out of eleven are more evolved objects (5x10^6-10^7 yr), indicating that geometrical effects can significantly modify the SED shapes. Inferred mass accretion rates (Macc) show a wide range of values (3.6x10^-9 to 1.2x10^-5 M_sun yr^-1), which reflects the age spread observed in our sample. Average values of mass accretion rates, extinction, and spectral indices decrease with the YSO class. The youngest YSOs have the highest Macc, whereas the oldest YSOs do not show any detectable jet activity in either images and spectra. We also observe a clear correlation among the YSO Macc, M*, and age, consistent with mass accretion evolution in viscous disc models.Comment: 61 pages, 16 figures; A&A in pres

Six Human-Centered Artificial Intelligence Grand Challenges

Widespread adoption of artificial intelligence (AI) technologies is substantially affecting the human condition in ways that are not yet well understood. Negative unintended consequences abound including the perpetuation and exacerbation of societal inequalities and divisions via algorithmic decision making. We present six grand challenges for the scientific community to create AI technologies that are human-centered, that is, ethical, fair, and enhance the human condition. These grand challenges are the result of an international collaboration across academia, industry and government and represent the consensus views of a group of 26 experts in the field of human-centered artificial intelligence (HCAI). In essence, these challenges advocate for a human-centered approach to AI that (1) is centered in human well-being, (2) is designed responsibly, (3) respects privacy, (4) follows human-centered design principles, (5) is subject to appropriate governance and oversight, and (6) interacts with individuals while respecting human’s cognitive capacities. We hope that these challenges and their associated research directions serve as a call for action to conduct research and development in AI that serves as a force multiplier towards more fair, equitable and sustainable societies

Prognostic role of endocarditis in isolated tricuspid valve surgery. A propensity-weighted study

Objectives The role of the underlying etiology in isolated tricuspid valve surgery has not been investigated extensively in current literature. Aim of this study was to analyse outcomes of patients undergoing surgery due to endocarditis compared to other pathologies. Methods The SURTRI study is a multicenter study enrolling adult patients who underwent isolated tricuspid valve surgery (n = 406, 55 ± 16 y.o.; 56% female) at 13 international sites. Propensity weighted analysis was performed to compare groups (IE group n = 107 vs Not-IE group n = 299). Results No difference was found regarding the 30-day mortality (Group IE: 2.8% vs Group Not-IE = 6.8%; OR = 0.45) and major adverse events. Weighted cumulative incidence of cardiac death was significantly higher for patients with endocarditis (p = 0.01). The composite endpoint of cardiac death and reoperation at 6 years was reduced in the Group IE (63.2 ± 6.8% vs 78.9 ± 3.1%; p = 0.022). Repair strategy resulted in an increased late survival even in IE cases. Conclusions Data from SURTRI study report acceptable 30-day results but significantly reduced late survival in the setting of endocarditis of the tricuspid valve. Multi-disciplinary approach, repair strategy and earlier treatment may improve outcomes. © 2022 The Author

Pattern of reading eye movements during monovision contact lens wear in presbyopes

Monovision can be used as a method to correct presbyopia with contact lenses (CL) but its effect on reading behavior is still poorly understood. In this study eye movements (EM) were recorded in fifteen presbyopic participants, naïve to monovision, whilst they read arrays of words, non-words, and text passages to assess whether monovision affected their reading. Three conditions were compared, using daily disposable CLs: baseline (near correction in both eyes), conventional monovision (distance correction in the dominant eye, near correction in the non-dominant eye), and crossed monovision (the reversal of conventional monovision). Behavioral measures (reading speed and accuracy) and EM parameters (single fixation duration, number of fixations, dwell time per item, percentage of regressions, and percentage of skipped items) were analyzed. When reading passages, no differences in behavioral and EM measures were seen in any comparison of the three conditions. The number of fixations and dwell time significantly increased for both monovision and crossed monovision with respect to baseline only with word and non-word arrays. It appears that monovision did not appreciably alter visual processing when reading meaningful texts but some limited stress of the EM pattern was observed only with arrays of unrelated or meaningless items under monovision, which require the reader to have more in-depth controlled visual processing

Compulsory and recommended vaccination in Italy: evaluation of coverage and non-compliance between 1998-2002 in Northern Italy

BACKGROUND: Since vaccinations are an effective prevention tool for maintaining the health of society, the monitoring of immunization coverage allows us to identify areas where disease outbreaks are likely to occur, and possibly assist us in predicting future outbreaks. The aim of this study is the investigation of the coverage achieved for compulsory (diphtheria, tetanus, polio, hepatitis B,) and recommended (pertussis, Haemophilus influenzae, measles-mumps-rubella) vaccinations between 1998 and 2002 in the municipality of Bologna and the identification of the subjects not complying with compulsory and recommended vaccinations. METHODS: The statistics regarding vaccinal coverage were elaborated from the data supplied by the Bologna vaccinal registration system (1998–2000) and the IPV4 program (2001–2002). To calculate the coverage for compulsory vaccinations and cases of non-compliance reference was made to the protocol drawn up by the Emilia Romagna Regional Administration. The reasons for non-compliance were divided into various categories RESULTS: In Bologna the levels of immunization for the four compulsory vaccinations are satisfactory: over 95% children completed the vaccinal cycle, receiving the booster for anti-polio foreseen in their 3(rd )year and for anti-dyphteria, tetanus, pertussis at 6 years. The frequency of subjects with total non-compliance (i.e. those who have not begun any compulsory vaccinations by the age of one year) is generally higher in Bologna than in the region, with a slight increase in 2002 (2.52% and 1.06% in the city and the region respectively). The frequency of the anti-measles vaccination is higher than that of mumps and rubella, which means that the single vaccine, as opposed to the combined MMR (measles-mumps-rubella) was still being used in the period in question. The most common reason for non compliance is objection of parents and is probably due to reduction of certain diseases or anxiety about the possible risks. CONCLUSION: In Bologna the frequency of children aged 12 and 24 months who have achieved compulsory vaccination varied, in 2002, between 95% and 98%. As regards recommended vaccinations the percentage of coverage against Haemophilus influenzae is 93.3%, while the levels for measles, mumps and pertussis range from 84% to approx. 92%. Although these percentages are higher if compared to those obtained by other Italian regions, every effort should be made to strengthen the aspects that lead to a successful vaccinal strategy

Adolescentes y drogas : su relación con la delincuencia

Esta investigación describe la relación con las drogas de una muestra de 286 Adolescentes en Conflicto con la Ley de la ciudad de Valencia (España). Tiene por objeto analizar relación entre trayectoria delictiva y consumo de drogas. Los resultados informan que a mayor incidencia delictiva, mayor dependencia. En cuanto a patrones de consumo por tipo de sustancia, el cannabis se asocia a trayectorias delictivas iniciales y la cocaína a trayectorias consolidadas. El consumo se produce en escenarios habituales diurnos, se extiende a otros de ocio nocturno, y particularmente forma parte de la vida cotidiana de los adolescentes en conflicto con la ley de trayectoria consolidada