Etiolation and flooding of donor plants enhance the capability of Arabidopsis explants to root

Rooting of cuttings depends not only on the rooting treatment and the genotype, but also on the condition of the cuttings at the time of excision. The physiological and developmental conditions of the donor plant may be decisive. We have examined in Arabidopsis the effect of two donor plant pre-treatments, etiolation and flooding, on the capability of flower stem and hypocotyl segments to root. For etiolation, plantlets were kept in the dark, hypocotyls up to 12 days and plantlets for 12 weeks. Flooding was applied as a layer of liquid medium on top of the semi-solid medium. This procedure is also referred to as “double layer”. Both pre-treatments strongly promoted rooting and we examined possible mechanisms. Expression of strigolactone biosynthesis and signaling related genes indicated that promotion by etiolation may be related to enhanced polar auxin transport. Increased rooting after flooding may have been brought about by accumulation of ethylene in the cutting (ethylene has been reported to increase sensitivity to auxin) and by massive formation of secondary phloem (the tissue close to which adventitious roots are induced). Both pre-treatments also strongly lowered the endogenous sucrose level. As low sucrose favors the juvenile state and juvenile tissues have a higher capability to root, the low sucrose levels may also play a role

The effect of proactive versus reactive treatment of hypotension on postoperative disability and outcome in surgical patients under anaesthesia (PRETREAT): clinical trial protocol and considerations

Background: Intraoperative hypotension has been extensively studied for its association with adverse outcomes. However, small sample sizes and methodological issues limit the causal inference that can be drawn. Methods: In this multicentre, adaptive, randomised controlled trial, we will include 5000 adult inpatients scheduled for elective non-cardiac surgery under general or central neuraxial anaesthesia. Patients will be either randomly allocated to the intervention or care-as-usual group using computer-generated blocks of four, six, or eight, with an allocation ratio of 1:1. In the intervention arm patients will be divided into low-, intermediate-, and high-risk groups based on their likelihood to experience intraoperative hypotension, with resulting mean blood pressure targets of 70, 80, and 90 mm Hg, respectively. Anaesthesia teams will be provided with a clinical guideline on how to keep patients at their target blood pressure. During the first 6 months of the trial the intervention strategy will be evaluated and further revised in adaptation cycles of 3 weeks if necessary, to improve successful impact on the clinical process. The primary outcome is postoperative disability after 6 months measured with the World Health Organization Disability Assessment Score (WHODAS) 2.0 questionnaire. Ethics and dissemination: This study protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht (20–749) and all protocol amendments will be communicated to the Medical Ethics Committee. The study protocol is in adherence with the Declaration of Helsinki and the guideline of Good Clinical Practice. Dissemination plans include publication in a peer-reviewed journal. Clinical trial registration: The Dutch Trial Register, NL9391. Registered on 22 March 2021

Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era

Background: Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy. Methods: Two hundred and eighty-one dMMR mCRC patients (n = 54 from three prospective Phase 3 CAIRO trials; n = 227 from the Netherlands Cancer Registry). Overall survival was analysed from diagnosis of mCRC (OS), from initiation of first-line (OS1) and second-line (OS2) systemic treatment. Cox regression analysis examined prognostic factors. As comparison for OS 2746 MMR proficient mCRC patients were identified. Results: Of 281 dMMR patients, 62% received first-line and 26% second-line treatment. Median OS was 16.0 months (13.8–19.6) with antitumour therapy and 2.5 months (1.8–3.5) in untreated patients. OS1 was 12.8 months (10.7–15.2) and OS2 6.2 months (5.4–8.9) in treated dMMR patients. Treated dMMR patients had a 7.6-month shorter median OS than pMMR patients. Conclusion: Available data from immunotherapy trials lack a control arm with standard systemic treatment. Given the poor outcome compared to the immunotherapy results, our data strongly suggest a survival benefit of immunotherapy in dMMR mCRC patients