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Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y12 inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose. A total of 14 963 patients treated with DAPT after coronary stenting—largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation—were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12–24 months) or short (3–6 months) treatment in relation to baseline bleeding risk. The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0·73 (95% CI 0·61–0·85) in the derivation cohort, and 0·70 (0·65–0·74) in the PLATO trial validation cohort and 0·66 (0·61–0·71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score ≥25), but not in those with lower risk profiles (pinteraction=0·007), and exerted a significant ischaemic benefit only in this latter group. The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration. None.

BackgroundUpper gastrointestinal (GI) bleeding following transcatheter aortic valve replacement (TAVR) is common in patients with aortic stenosis due to the combination of acquired type 2A von Willebrand disease and aspirin-based antiplatelet therapy. We aimed to investigate the incidence, predictors and clinical outcomes of late upper GI bleeding in patients undergoing TAVR.MethodsIn a prospective TAVR registry, patients were stratified according to upper GI bleeding within 1 year of discharge.ResultsAmong the 3144 eligible patients, 54 (1.7%) experienced upper GI bleeding after discharge. Of these, 40 patients had major or life-threatening bleeding, while 14 had minor bleeding events. The presence of atrial fibrillation or atrial flutter (HRadjusted 2.98; 95% CI 1.65 to 5.38) and previous upper GI bleeding (HRadjusted 3.51; 95% CI 1.51 to 8.19) were independent predictors of upper GI bleeding, while the use of proton pump inhibitors at discharge (HRadjusted 0.49; 95% CI 0.27 to 0.89) and higher haemoglobin levels (1 g/dL increase) (HRadjusted 0.73; 95% CI 0.62 to 0.87) were protective. Patients who experienced major or life-threatening upper GI bleeding had a higher all-cause (73.7% vs 11.4%, HR 5.84; 95% CI 3.41 to 10.02) and cardiovascular mortality (31.6% vs 7.3%, HR 3.87; 95% CI 1.72 to 8.70) compared with those without upper GI bleeding.ConclusionsAmong patients who underwent TAVR, 1.7% of patients experienced upper GI bleeding within 1 year of discharge. Major or life-threatening upper GI bleeding was associated with an increased risk of all-cause and cardiovascular mortality.Trial registration number NCT01368250.

Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent. We did a randomised, single-blind, non-inferiority trial with minimum exclusion criteria at nine hospitals in Switzerland. We randomly assigned (1:1) patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention to treatment with biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Randomisation was via a central web-based system and stratified by centre and presence of ST segment elevation myocardial infarction. Patients and outcome assessors were masked to treatment allocation, but treating physicians were not. The primary endpoint, target lesion failure, was a composite of cardiac death, target vessel myocardial infarction, and clinically-indicated target lesion revascularisation at 12 months. A margin of 3·5% was defined for non-inferiority of the biodegradable polymer sirolimus-eluting stent compared with the durable polymer everolimus-eluting stent. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01443104. Between Feb 24, 2012, and May 22, 2013, we randomly assigned 2119 patients with 3139 lesions to treatment with sirolimus-eluting stents (1063 patients, 1594 lesions) or everolimus-eluting stents (1056 patients, 1545 lesions). 407 (19%) patients presented with ST-segment elevation myocardial infarction. Target lesion failure with biodegradable polymer sirolimus-eluting stents (69 cases; 6·5%) was non-inferior to durable polymer everolimus-eluting stents (70 cases; 6·6%) at 12 months (absolute risk difference −0·14%, upper limit of one-sided 95% CI 1·97%, p for non-inferiority <0·0004). No significant differences were noted in rates of definite stent thrombosis (9 [0·9%] vs 4 [0·4%], rate ratio [RR] 2·26, 95% CI 0·70–7·33, p=0·16). In pre-specified stratified analyses of the primary endpoint, biodegradable polymer sirolimus-eluting stents were associated with improved outcome compared with durable polymer everolimus-eluting stents in the subgroup of patients with ST-segment elevation myocardial infarction (7 [3·3%] vs 17 [8·7%], RR 0·38, 95% CI 0·16–0·91, p=0·024, p for interaction=0·014). In a patient population with minimum exclusion criteria and high adherence to dual antiplatelet therapy, biodegradable polymer sirolimus-eluting stents were non-inferior to durable polymer everolimus-eluting stents for the combined safety and efficacy outcome target lesion failure at 12 months. The noted benefit in the subgroup of patients with ST-segment elevation myocardial infarction needs further study. Clinical Trials Unit, University of Bern, and Biotronik, Bülach, Switzerland.

We manipulated predation risk in a field experiment with the cooperatively breeding cichlid Neolamprologus pulcher by releasing no predator, a medium- or a large-sized fish predator inside underwater cages enclosing two to three natural groups. We assessed whether helpers changed their helping behaviour, and whether within-group conflict changed, depending on these treatments, testing three hypotheses: 'pay-to-stay' PS, 'risk avoidance' RA, or (future) reproductive benefits RB. We also assessed whether helper food intake was reduced under risk, because this might reduce investments in other behaviours to save energy. Medium and large helpers fed less under predation risk. Despite this effect helpers invested more in territory defence, but not territory maintenance, under the risk of predation (supporting PS). Experimentally covering only the breeding shelter with sand induced more helper digging under predation risk compared to the control treatment (supporting PS). Aggression towards the introduced predator did not differ between the two predator treatments and increased with group member size and group size (supporting PS and RA). Large helpers increased their help ratio (helping effort/breeder aggression received, 'punishment' by the dominant pair in the group) in the predation treatments compared to the control treatment, suggesting they were more willing to PS. Medium helpers did not show such effects. Large helpers also showed a higher submission ratio (submission/ breeder aggression received) in all treatments, compared to the medium helpers (supporting PS). We conclude that predation risk reduces helper food intake, but despite this effect, helpers were more willing to support the breeders, supporting PS. Effects of breeder punishment suggests that PS might be more important for large compared to the medium helpers. Evidence for RA was also detected. Finally, the results were inconsistent with RB.

Alloparental brood care, where individuals help raising the offspring of others, is generally believed to be favoured by high degrees of relatedness between helpers and recipients. Here we show that in cooperatively breeding cichlids, unrelated subordinate females provide more alloparental care than related ones when kinship between dominant and subordinate group members is experimentally manipulated. In addition, unrelated helpers increased alloparental care after we simulated egg cannibalism by helpers, an effect not shown by related helpers. By supporting predictions of pay-to-stay theory, these results suggest that in Neolamprologus pulcher , reciprocal commodity trading is important for the decision of subordinates to invest in care of the dominants’ offspring. In alloparental brood care, individuals help raise the offspring of others and it is thought that high relatedness between the helpers and recipients is needed. In contrast, Zöttl et al . find that, in cooperatively breeding cichlids, unrelated subordinate females provide more alloparental care than related ones.

An inflammatory process may increase the risk of arrhythmias after transcatheter aortic valve replacement (TAVR). In this single-centre, double-blind, placebo-controlled, randomized trial we investigated the efficacy of colchicine to reduce a composite of new-onset atrial fibrillation or atrioventricular conduction disturbances requiring the implantation of a permanent pacemaker at 30 days after TAVR. Between September 21, 2021 and April 25, 2024, 120 patients with aortic stenosis undergoing TAVR (mean age 80.6 ± 5 years, 64% male) were randomly allocated to treatment with colchicine ( n  = 60) or placebo ( n  = 60). The trial was prematurely stopped due to a higher rate of stroke in the experimental group in a pre-specified interim analysis (5 [8.3%] versus 0 at maximum available follow-up, p  = 0.022). In the intention-to-treat population, the primary endpoint occurred in 6 patients (10%) in the colchicine group and in 15 patients (25%) in the placebo group (risk-difference −15.0%, 95% CI −28.3 to −1.7, p  = 0.031). The prespecified imaging endpoint, subclinical leaflet thrombosis, was detected in 13 of 48 patients (27%) in the colchicine group versus 26 of 48 patients (54%) in the placebo group (risk difference −27.1%. 95% CI −46.0% to −8.2%, p  = 0.007). Here, we show that periprocedural treatment with colchicine may reduce the incidence of new-onset arrhythmias and subclinical leaflet thrombosis after TAVR. However, given the premature termination of the trial due to an unexpected increase in the stroke rate among patients treated with colchicine, confirmatory trials are warranted to corroborate the effect of anti-inflammatory treatment on the incidence of arrhythmias and subclinical leaflet thrombosis after TAVR. The trial was an investigator-initiated study supported by dedicated grants from the Bangerter-Rhyner Foundation and the Swiss Life Foundation. ClinicalTrials.gov Identifier: NCT04870424. An inflammatory process may increase the risk of arrhythmias after transcatheter aortic valve replacement. Here, the authors show that periprocedural treatment with colchicine may reduce the incidence of new-onset arrhythmias and subclinical leaflet thrombosis after transcatheter aortic valve replacement.

B-type natriuretic peptide (BNP) levels are elevated in patients with aortic stenosis (AS) and decrease acutely after replacement of the stenotic valve. The long-term prognostic value of BNP after transcatheter aortic valve implantation (TAVI) and the relative prognostic utility of single versus serial peri-interventional measurements of BNP and N-terminal prohormone BNP (NT-pro-BNP) are unknown. This study sought to determine the impact of BNP levels on long-term outcomes after TAVI and to compare the utility of BNP versus NT-pro-BNP measured before and after intervention. We analyzed 340 patients with severe AS and baseline pre-TAVI assessment of BNP. In 219 patients, BNP and NT-pro-BNP were measured serially before and after intervention. Clinical outcomes over 2 years were recorded. Patients with high baseline BNP (higher tertile ≥591 pg/ml) had increased risk of all-cause mortality (adjusted hazard ratio 3.16, 95% confidence interval 1.84 to 5.42; p <0.001) and cardiovascular death at 2 years (adjusted hazard ratio 3.37, 95% confidence interval 1.78 to 6.39; p <0.001). Outcomes were most unfavorable in patients with persistently high BNP before and after intervention. Comparing the 2 biomarkers, NT-pro-BNP levels measured after TAVI showed the highest prognostic discrimination for 2-year mortality (area under the curve 0.75; p <0.01). Baseline-to-discharge reduction, but not baseline levels of BNP, was related to New York Heart Association functional improvement. In conclusion, high preintervention BNP independently predicts 2-year outcomes after TAVI, particularly when elevated levels persist after the intervention. BNP and NT-pro-BNP and their serial periprocedural changes provide complementary prognostic information for symptomatic improvement and survival.

Among patients undergoing transcatheter aortic valve implantation (TAVI), concomitant mitral regurgitation (MR) has been associated with adverse prognosis. We aimed to assess long-term clinical outcomes according to MR etiology. In a single-center registry of consecutive patients undergoing TAVI, we investigated the impact of functional (FMR) vs degenerative (DMR) MR on cardiovascular (CV) mortality throughout 2years of follow-up. Among 603 patients (mean age 82.4±5.7years, 55% female) undergoing TAVI, 149 patients had moderate or severe MR (24.7%). Functional MR and DMR were documented in 53 (36%) and 96 (64%) patients, respectively. At 2years, patients with FMR and DMR had higher rates of CV mortality (30.2% vs 32.4%) as compared with patients with no MR (14.6%; FMR vs no MR: hazard ratio [HR] 2.32, 95% CI 1.34-4.02, P=.003; DMR vs no MR: HR 2.56, 95% CI 1.66-3.96, P<.001). In adjusted analyses, DMR was associated with an increased risk of CV mortality throughout the 2-year follow-up (adjusted HR 2.21, 95% CI 1.4-3.49, P=.001) as compared with FMR (adjusted HR 1.13, 95% CI 0.59-2.18, P=.707). Relevant MR was postprocedurally significantly reduced in both the DMR and FMR groups, whereas improvement of a decreased left ventricular ejection fraction was predominantly seen in the FMR group as compared with baseline. Patients with severe, symptomatic aortic stenosis undergoing TAVI complicated by moderate or severe MR portend impaired prognosis. Particularly, patients with DMR are at increased risk for CV mortality during long-term follow-up.

Phenotypic plasticity is a crucial mechanism for responding to changes in climatic means, yet we know little about its role in responding to extreme climatic events (ECEs). ECEs may lack the reliable cues necessary for phenotypic plasticity to evolve; however, this has not been empirically tested. We investigated whether behavioural plasticity in nest-site selection allows a long-lived shorebird (Haematopus ostralegus) to respond to flooding. We collected longitudinal nest elevation data on individuals over two decades, during which time flooding events have become increasingly frequent. We found no evidence that individuals learn from flooding experiences, showing nest elevation change consistent with random nest-site selection. There was also no evidence of phenotypic plasticity in response to potential environmental cues (lunar nodal cycle and water height). A small number of individuals, those nesting near an artificial sea wall, did show an increase in nest elevation over time; however, there is no conclusive evidence this occurred in response to ECEs. Our study population showed no behavioural plasticity in response to changing ECE patterns. More research is needed to determine whether this pattern is consistent across species and types of ECEs. If so, ECEs may pose a major challenge to the resilience of wild populations. This article is part of the themed issue ‘Behavioural, ecological and evolutionary responses to extreme climatic events’.

The effectiveness of durable polymer drug-eluting stents comes at the expense of delayed arterial healing and subsequent late adverse events such as stent thrombosis (ST). We report the 4 year follow-up of an assessment of biodegradable polymer-based drug-eluting stents, which aim to improve safety by avoiding the persistent inflammatory stimulus of durable polymers. We did a multicentre, assessor-masked, non-inferiority trial. Between Nov 27, 2006, and May 18, 2007, patients aged 18 years or older with coronary artery disease were randomly allocated with a computer-generated sequence to receive either biodegradable polymer biolimus-eluting stents (BES) or durable polymer sirolimus-eluting stents (SES; 1:1 ratio). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR); patients were followed-up for 4 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389220. 1707 patients with 2472 lesions were randomly allocated to receive either biodegradable polymer BES (857 patients, 1257 lesions) or durable polymer SES (850 patients, 1215 lesions). At 4 years, biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18·7%) patients versus 192 (22·6%) patients (rate ratios [RR] 0·81, 95% CI 0·66–1·00, p for non-inferiority <0·0001, p for superiority=0·050). The RR of definite ST was 0·62 (0·35–1·08, p=0·09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0·20, 95% CI 0·06–0·67, p=0·004). Conversely, the RR of definite ST during the first year was 0·99 (0·51–1·95; p=0·98) and the test for interaction between RR of definite ST and time was positive ( p interaction=0·017). We recorded an interaction with time for events associated with ST but not for other events. For primary endpoint events associated with ST, the RR was 0·86 (0·41–1·80) during the first year and 0·17 (0·04–0·78) during subsequent years ( p interaction=0·049). Biodegradable polymer BES are non-inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES. Biosensors Europe SA, Switzerland.