Background: The prevalence of intracranial aneurysm in patients with autosomal dominant polycystic kidney disease (ADPKD) is higher than that among the general population. We performed a systematic review and meta-analysis on the prevalence and natural history of intracranial aneurysm among patients with ADPKD. Methods: Medline, Embase, Web of Science and Scopus, from inception to July 2016, were searched for studies reporting the occurrence of intracranial aneurysms among participants with ADPKD. Two authors independently assessed the eligibility of all retrieved studies and extracted data. Information on the prevalence of intracranial aneurysms and their natural history in participants with ADPKD was collected from all included studies. Results: Fifteen studies with 1,490 participants with ADPKD were pooled to study about the prevalence of intracranial aneurysm in participants with ADPKD, and the prevalence rate was found to be 10% (95% CI 7-13%). Studies from China, Japan and Europe (Germany, Poland) reported a higher prevalence of intracranial aneurysm. Having a family history of haemorrhagic stroke or intracranial aneurysm was a risk factor for aneurysm occurrence. Twenty-three percent (95% CI 15-31%) of the participants had multiple aneurysms. Most of the aneurysms were small (<6 mm) and located in the anterior circulation. Five studies with 171 participants (83 with 106 aneurysms at baseline and 88 without) were analyzed to understand the natural history of aneurysms, with an incidence of aneurysm growth, new aneurysm and aneurysm rupture of 1.84% (followed up for 435 person-years), 0.57% (1,227 person-years) and 0.13% (792 person-years) respectively. Conclusions: Screening for intracranial aneurysm is recommended in patients with ADPKD when there is a family history of haemorrhagic stroke or intracranial aneurysm and when they are from China, Japan or Europe (Germany, Poland). Based on existing data, regular imaging follow-up is not supported. High-quality, prospective studies are needed in the future.

ObjectiveTo determine the adverse outcomes following resumption of anticoagulation in patients with anticoagulation-associated intracranial haemorrhage (ICH).DesignWe performed a systematic review and meta-analysis in this clinical population. The Preferred Reporting Items for Systemic Reviews and Meta-Analyses statement was followed, and two authors independently assessed eligibility of all retrieved studies and extracted data.Data sourcesMedline, Embase and the Cochrane Central Register of Controlled Trials, from inception to February 2017.Eligibility criteria and outcomesRandomised controlled trials or cohort studies that recruited adults who received oral anticoagulants at the time of ICH occurrence and survived after the acute phase or hospitalisation were searched. Primary outcomes, including long-term mortality, recurrent ICH and thromboembolic events. Secondary outcomes were the frequency of resuming anticoagulant therapy and related factors.ResultsWe included 12 cohort studies (no clinical trials) involving 3431 ICH participants. The pooled frequency of resuming anticoagulant therapy was 38% (95% CI 32% to 44%), but this was higher in participants with prosthetic heart valves, subarachnoid haemorrhage or dyslipidaemia. There was no evidence that resuming anticoagulant therapy was associated with higher long-term mortality (pooled relative risk (RR) 0.60, 95% CI 0.30 to 1.19; p=0.14) or ICH recurrence (pooled RR 1.14, 95% CI 0.72 to 1.80; p=0.57). Resumption of anticoagulation was associated with significantly fewer thromboembolic events (pooled RR 0.31, 95% CI 0.23 to 0.42; p<0.001). In a subgroup of patients with atrial fibrillation, resuming anticoagulant therapy was associated with fewer long-term mortality (pooled RR 0.27, 95% CI 0.20 to 0.37, p<0.001).ConclusionsBased on these observational studies, resuming anticoagulant therapy after anticoagulation-associated ICH has beneficial effects on long-term complications. Clinical trials are needed to substantiate these findings.PROSPERO registration numberCRD42017063827.

We tested the hypothesis that pregnancy might increase diabetes-associated nitric oxide (NO) production and renal hyperfiltration. Two weeks following i.v. streptozotocin (40 mg/kg), mean arterial pressure (MAP) was not modified by diabetes; glomerular filtration rate (GFR), renal plasma flow (RPF) and filtration fraction (FF) were higher in pregnant than in virgin controls and increased by diabetes to a greater extent in pregnant than in virgin rats. Urinary volume (UV), creatinine, albumin and sodium (U Na V) were significantly increased by diabetes. Diabetes led to an increase in renal, cardiac, aortic and uterine but not in placental NO synthase activities. Infusion of N Gnitro--arginine (-NA) caused a dose-dependent reduction in GFR, RPF, plasma NO 2 /NO 3 , UV and U Na V; in general, diabetes increased these effects to a greater extent in pregnant than in virgin rats. -NA increased MAP in all groups of rats but did not alter FF. Diabetes did not alter responses of thoracic aorta rings to vasoconstrictor effects of phenylephrine and the vasorelaxant effects of sodium nitroprusside but increased endothelium-dependent relaxant effects of acetylcholine. In general the effects of diabetes of 7 days duration were similar to those described above for diabetes of 14 days duration. These data suggest that diabetes-associated renal hyperfiltration and NO production are augmented by pregnancy.

Graft-versus-host disease (GVHD) is the major complication after allogeneic bone marrow transplantation. Valproic acid (VPA) was described as a histone deacetylase inhibitor that had anti-inflammatory effects and reduced the production of proinflammatory cytokines in experimental autoimmune disease models. Using well-characterized mouse models of MHC-mismatched transplantation, we studied the effects of VPA on GVHD severity and graft-versus-leukemia (GVL) activity. Administration of VPA significantly attenuated the clinical severity of GVHD, the histopathology of GVHD-involved organs, and the overall mortality from GVHD. VPA downregulated Th1 and Th17 cell responses and cytokine production in vitro and in vivo, whereas its effect on GVHD was regulatory T cell independent. The effect of VPA was related to its ability to directly reduce the activity of Akt, an important regulator of T cell immune responses. Importantly, when mice received lethal doses of host-type acute leukemia cells, administration of VPA did not impair GVL activity and resulted in significantly improved leukemia-free survival. These findings reveal a unique role for VPA as a histone deacetylase inhibitor in reducing the donor CD4+ T cells that contribute to GVHD, which may provide a strategy to reduce GVHD while preserving the GVL effect.

Compared to cystatin C, Gas6 may be potentially a better noninvasive diagnostic biomarker for early detection of DN.