LAR continues to provide a risk to patient and graft survival: understanding risk factors may allow an improvement in monitoring and early intervention and so prevent early graft loss.

Summary Background Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. Funding British Heart Foundation.

Regulation of attachment of equine spermatozoa to homologous oviduct epithelium was investigated by co-culture of spermatozoa with oviductal epithelial cell explants. Stallion spermatozoa were incubated with explants derived from the isthmus and ampulla of follicular, postovulatory, and diestrous mares. Steroid treatments (estradiol, progesterone, or control) were applied across all explant groups. Estimates of motility and total numbers of attached spermatozoa were made 0.5, 24, and 48 h after initiation of co-culture. Equine spermatozoa attached by their rostral acrosomal region to both ciliated and nonciliated oviduct epithelial cells. Steroid treatment had no effect on either motility or total number of attached spermatozoa. Motility of spermatozoa attached to ampullar and isthmic explants did not differ. However, at both 24 h and 48 h, motility of spermatozoa attached to follicular-stage explants exceeded that of spermatozoa attached to postovulatory or diestrous-stage explants (p < 0.05). The number of spermatozoa that bound to explants was affected by stage of cycle, anatomic origin of explant, and time in co-culture (p < 0.001), as well as the interaction of cycle stage, anatomic origin, and time in co-culture (p < 0.001). More spermatozoa bound to explants of isthmic than ampullar origin, and more spermatozoa bound to follicular and postovulatory explants than to diestrous explants (p < 0.05). These data support the existence of a spermatozoal reservoir in the oviductal isthmus of the mare and suggest that there may be cycle stage-specific regulation of both motility and the number of spermatozoa attached to oviductal epithelium.

EBK had the best long-term outcomes among deceased donor transplants and offer unique options for adult kidney transplant recipients.

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Attachment of spermatozoa to oviductal epithelial cells (OEC) may be a prefertilization event in some species. We tested the hypothesis that spermatozoa that attach to equine OEC monolayers are a selected subpopulation of the initial inseminate, containing a higher proportion of morphologically normal, motile cells than the inseminate. Washed stallion spermatozoa were cocultured with monolayers of OEC or monolayers of Vero cells, and controls were incubated in wells coated with basement membrane extract (Matrigel [Mgel]) or in plastic (uncoated) wells. Unattached spermatozoa were removed by rinsing at 0.5 h of coculture. Spermatozoa that attached and subsequently released were collected at 3 h. Total cell numbers and percentages of motile, viable, and morphologically normal spermatozoa were counted in the initial inseminate, in plastic control wells, and in the coculture supernatants after incubation. The percentages of motile and morphologically normal spermatozoa attached to OEC, Mgel control wells, and Vero cell cocultures were measured in situ after 0.5 and 3 h of incubation. Populations of spermatozoa that attached to either OEC or Mgel had higher motility and those attached to OEC contained a higher percentage of normal spermatozoa than the inseminate. Compared to the inseminate, populations that did not attach had similar viability and contained a similar percentage of normal spermatozoa, but had lower motility. Spermatozoal populations released (at 3 h) were similar in percentage of normal morphology to those that were attached, but exhibited reduced motility and viability when compared to the inseminate. We noted no difference in motility or morphology between populations of spermatozoa attached to OEC and those attached to Vero cell monolayers.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy. Methods RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627.