SummaryBackgroundRemote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months.MethodsWe did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed.FindingsBetween Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91–1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed.InterpretationRemote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI.FundingBritish Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

The condition known as cryptorchidism – undescended testis – is one of the most common congenital abnormalities found among males, and is one of the few known risk factors for testicular cancer (TC). Like testicular cancer, the key exposures in the occurrence of cryptorchidism remain elusive. Testicular descent is thought to occur during two hormonally-controlled phases – between 8–15 weeks and 25–35 weeks gestation – and while it is clear that a failure of testes to descend permanently is likely due to disruptions to one or both of these phases, the cause(s) and mechanism(s) of such disruption are still unclear. In this manuscript, we review the broad range of putative risk factors that have been evaluated in relation to the development of cryptorchidism to date, discuss their plausibility, and make suggestions regarding further approaches to understand aetiology. There are few exposures for which there is consistent evidence of an association with cryptorchidism; and in those cases where evidence appears unequivocal – for example, the relationship between cryptorchidism and gestational measures such as low birth weight – the measured exposure is likely to be a surrogate for the true causal exposure. The relative importance of each risk factor may vary considerably between mother/son pairs depending on an array of genetic, maternal, placental and foetal factors – all of which could vary between regions.

BackgroundThe aetiology of testicular cancer remains elusive. In this manuscript, we review the evidence regarding the association between cannabis use and testicular cancer development.MethodsIn this systematic review and meta-analysis, we reviewed literature published between 1st January 1980 and 13th May 2015 and found three case–control studies that investigated the association between cannabis use and development of testicular germ cell tumours (TGCTs).Results/ConclusionsUsing meta-analysis techniques, we observed that a) current, b) chronic, and c) frequent cannabis use is associated with the development of TGCT, when compared to never-use of the drug. The strongest association was found for non-seminoma development – for example, those using cannabis on at least a weekly basis had two and a half times greater odds of developing a non-seminoma TGCT compared those who never used cannabis (OR: 2.59, 95 % CI 1.60–4.19). We found inconclusive evidence regarding the relationship between cannabis use and the development of seminoma tumours. It must be noted that these observations were derived from three studies all conducted in the United States; and the majority of data collection occurred during the 1990’s.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1905-6) contains supplementary material, which is available to authorized users.

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Tobacco explains many of the social group trends and differences and constitutes an inequity. Cervical cancer trends are plausibly explained by screening and sexual practices. Faster increases of colorectal and breast cancer among Māori are presumably due to changes in dietary and reproductive behaviour, but the higher Māori breast cancer rate is unexplained. Ethnic differences in bladder, brain, endometrial and kidney cancer cannot be fully explained.