Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19thFeb 2018. Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible.Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1. Results: As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median duration of response (DoR) and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in ≥ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients. Conclusions: TRK fusions are detected in a broad range of tumor types. Larotrectinib is an effective age- and tumor-agnostic treatment for TRK fusion cancer with a positive safety profile. Screening patients for NTRK gene fusions in solid- and brain tumors should be actively considered

Emergence of classicality in small number entangled systems

We show the transition from a fully quantized interaction to a semiclassical one in entangled small number quantum systems using the quantum trajectories approach. In particular, we simulate the microwave Ramsey zones used in Rydberg atom interferometry, filling in the gap between the strongly entangling Jaynes Cummings evolution and the semiclassical rotation of the atomic internal states. We also correlate the information flowing with leaking photons to the entanglement generation between cavity field and flying atom and detail the roles played by the strong dissipation and the external driving force in preserving atomic coherence through the interaction.Comment: 4 pages, 6 figure

Comparison of diverse methods for the correction of atmospheric effects on LANDSAT and SKYLAB images

Earth's atmosphere reduces a sensors ability in currently discriminating targets. Using radiometric correction to reduce the atmospheric effects may improve considerably the performance of an automatic image interpreter. Several methods for radiometric correction from the open literature are compared leading to the development of an atmospheric correction system

Multicenter survey on the use of device-assisted enteroscopy in Portugal

Background: Device-assisted enteroscopies (DAEs) are recent endoscopic techniques that enable direct endoscopic smallbowel evaluation. Objective: The objective of this article is to evaluate the implementation of DAEs in Portugal and assess the main indications, diagnoses, diagnostic yield, therapeutic yield and complication rate. Methods: We conducted a multicenter retrospective series using a national Web-based survey on behalf of the Portuguese Small-Bowel Study Group. Participants were asked to fill out two online databases regarding procedural data, indications, diagnoses, endoscopic therapy and complications using prospectively collected institutional data records. Results: A total of eight centers were enrolled in the survey, corresponding to 1411 DAEs. The most frequent indications were obscure gastrointestinal bleeding (OGIB), inflammatory bowel disease and small-bowel tumors. The pooled diagnostic yield was 63%. A relation between the diagnostic yield and the indications was clear, with a diagnostic yield for OGIB of 69% (p ¼ 0.02) with a 52% therapeutic yield. Complications occurred in 1.2%, with a major complication rate of 0.57%. Perforations occurred in four patients (0.28%). Conclusion: DAEs are safe and effective procedures, with complication rates of 1.2%, the most serious of which is perforation. Most procedures are performed in the setting of OGIB. Diagnostic and therapeutic yields are dependent on the indication, hence appropriate patient selection is crucial.info:eu-repo/semantics/publishedVersio

Prevalence and risk factors for mental health problems in university undergraduate students : a systematic review with meta-analysis

Background: Effective targeting of services requires that we establish which undergraduates are at increased risk of mental health problems at university. We aimed to conduct a systematic review and meta-analysis of the prevalence and risk factors for mental health problems in undergraduates. Methods: We searched MEDLINE, PsycInfo, EMBASE and the Cochrane Central Register. Eligible studies were assessed using the Quality of Prognostic Studies checklist and narratively synthesised. Pooled prevalence of depression and suicide-related outcomes, and associated risk factors (odds ratios) were estimated using random-effects meta-analyses. Results: Sixty-six eligible studies of varying quality were included in a narrative synthesis. The pooled prevalence of depression (eight studies; 13,790 participants) was 25% (95% CI 17%, 35%) and the pooled prevalence of suicide-related outcomes (four studies; 2,586 participants) was 14% (95% CI 0%, 44%). Thirteen studies contributed to meta-analytic syntheses of 12 depression-related and four suicide-related risk factors. Presenting with a current mental health problem, negative rumination, parent separation, experiences of sexual harassment and parental depression significantly predicted depression outcomes. Childhood adversity, baseline mental health problems and financial difficulties significantly predicted suicide-related outcomes. Limitations: Student mental health is a heterogeneous research area and is hampered by the use of imprecise terms, both for describing risk factors and mental health outcomes. These inconsistencies limit the extent to which datasets can be meaningfully synthesised. Conclusions: This review evidences the importance of a range of risk factors for poor undergraduate mental health. Interventions should be developed to target modifiable risk factors and prevent poor mental health outcomes. Systematic review registration: PROSPERO registration CRD4201914492

In silico, in vitro and in vivo toxicological assessment of BPP-BrachyNH2, A vasoactive proline-rich oligopeptide from Brachycephalus ephippium.

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Small Bowel Enteroscopy - A Joint Clinical Guideline by the Spanish and Portuguese Small-Bowel Study Groups

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small-bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication, and its diagnostic and therapeutic yield. A set of recommendations was issued accordingly.info:eu-repo/semantics/publishedVersio