Is Regular Screening for Intracranial Aneurysm Necessary in Patients with Autosomal Dominant Polycystic Kidney Disease? A Systematic Review and Meta-analysis.

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.

Valproic Acid Ameliorates Graft-versus-Host Disease by Downregulating Th1 and Th17 Cells.

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.

Growth arrest-specific protein 6 (Gas6) as a noninvasive biomarker for early detection of diabetic nephropathy.

BACKGROUND: To investigate the diagnostic level of cystatin C and growth arrest-specific gene 6 (Gas6) levels in elderly type 2 diabetic patients with different degrees of diabetic nephropathy (DN). METHODS: Four hundred and eighty-two old people, including 130 healthy controls, 130 normoalbuminuric diabetic patients, 122 with microalbuminuria, and 100 with macroalbuminuria, were recruited. Plasma Gas6 and serum cystatin C levels were measured. RESULTS: Plasma Gas6 concentration was significantly lower in diabetic patients with microalbuminuria or macroalbuminuria, as compared with diabetic subjects with normoalbuminuria; while cystatin C was significantly higher. Gas6 was inversely correlated with BMI, WHR, and HbA1c, while cystatin C was inversely correlated with urea nitrogen and creatinine. Multivariate logistic regression analysis showed that, after adjusted for established diabetes risk factors, higher plasma Gas6 was significantly associated with a decreased risk of DN, while higher serum cystatin C was significantly associated with an increased risk. Receiver operating characteristic curve analysis showed that Gas6 was better than cystatin C as a biomarker for early diagnosis and detection of DN, with a cutoff value of 9.435 ng/mL (86.1% sensitivity and 84.6% specificity). CONCLUSION: Compared to cystatin C, Gas6 may be potentially a better noninvasive diagnostic biomarker for early detection of DN.

Social behavioral testing and brain magnetic resonance imaging in chicks exposed to mobile phone radiation during development.

BACKGROUND: The potential adverse effect of mobile phone radiation is currently an area of great concern in the field of public health. In the present study, we aimed to investigate the effect of mobile phone radiation (900 MHz radiofrequency) during hatching on postnatal social behaviors in chicks, as well as the effect on brain size and structural maturity estimated using 3.0 T magnetic resonance imaging. At day 4 of incubation, 76 normally developing chick embryos were divided into the control group (n = 39) and the radiation group (n = 37). Eggs in the radiation group were exposed to mobile phone radiation for 10 h each day from day 4 to 19 of incubation. Behavioral tests were performed 4 days after hatching. T2-weighted MR imaging and diffusion tensor imaging (DTI) were subsequently performed. The size of different brain subdivisions (telencephalon, optic lobe, brain stem, and cerebellum) and corresponding DTI parameters were measured. The Chi-square test and the student's t test were used for statistical analysis. P < 0.05 was considered statistically significant. RESULTS: Compared with controls, chicks in the radiation group showed significantly slower aggregation responses (14.87 ± 10.06 vs. 7.48 ± 4.31 s, respectively; P < 0.05), lower belongingness (23.71 ± 8.72 vs. 11.45 ± 6.53 s, respectively; P < 0.05), and weaker vocalization (53.23 ± 8.60 vs. 60.01 ± 10.45 dB/30 s, respectively; P < 0.05). No significant differences were found between the radiation and control group for brain size and structural maturity, except for cerebellum size, which was significantly smaller in the radiation group (28.40 ± 1.95 vs. 29.95 ± 1.41 cm(2), P < 0.05). The hatching and heteroplasia rates were also calculated and no significant difference was found between the two groups. CONCLUSIONS: Mobile phone radiation exposure during chick embryogenesis impaired social behaviors after hatching and possibly induced cerebellar retardation. This indicates potential adverse effects of mobile phone radiation on brain development.

Monitoring brain development of chick embryos in vivo using 3.0 T MRI: subdivision volume change and preliminary structural quantification using DTI.

BACKGROUND: Magnetic resonance imaging (MRI) has many advantages in the research of in vivo embryonic brain development, specifically its noninvasive aspects and ability to avoid skeletal interference. However, few studies have focused on brain development in chick, which is a traditional animal model in developmental biology. We aimed to serially monitor chick embryo brain development in vivo using 3.0 T MRI. METHODS: Ten fertile Hy-line white eggs were incubated and seven chick embryo brains were monitored in vivo and analyzed serially from 5 to 20 days during incubation using 3.0 T MRI. A fast positioning sequence was pre-scanned to obtain sagittal and coronal brain planes corresponding to the established atlas. T2-weighted imaging (T2WI) was performed for volume estimation of the whole brain and subdivision (telencephalon, cerebellum, brainstem, and lateral ventricle [LV]); diffusion tensor imaging (DTI) was used to reflect the evolution of neural bundle structures. RESULTS: The chick embryos' whole brain and subdivision grew non-linearly over time; the DTI fractional anisotropy (FA) value within the telencephalon increased non-linearly as well. All seven scanned eggs hatched successfully. CONCLUSIONS: MRI avoids embryonic sacrifice in a way that allows serial monitoring of longitudinal developmental processes of a single embryo. Feasibility for analyzing subdivision of the brain during development, and adding structural information related to neural bundles, makes MRI a powerful tool for exploring brain development.

Resuming anticoagulants after anticoagulation-associated intracranial haemorrhage: systematic review and meta-analysis.

OBJECTIVE: To determine the adverse outcomes following resumption of anticoagulation in patients with anticoagulation-associated intracranial haemorrhage (ICH). DESIGN: We 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 SOURCES: Medline, Embase and the Cochrane Central Register of Controlled Trials, from inception to February 2017. ELIGIBILITY CRITERIA AND OUTCOMES: Randomised 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. RESULTS: We 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). CONCLUSIONS: Based 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 NUMBER: CRD42017063827.

The superiority of allogeneic hematopoietic stem cell transplantation from unrelated donor over chemotherapy for adult patients with high-risk acute lymphoblastic leukemia in first remission.

For adult patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation(allo-HSCT) from HLA-matched related donors(MSD) is recommended for standard and high-risk patients. The role of unrelated donor transplantation (URD) in first remission has not been fully determined. We sought to compare directly the outcome of URD allo-HSCT and chemotherapy in patients with high-risk ALL. In this single center retrospective analysis, we included 74 consecutive adult patients with high-risk ALL in first complete remission(CR) and without a sibling donor, in which 32 patients received URD allo-HSCT in CR1 with busulfan-cyclophosphamide preparation regimen and in vivo T-cell depletion with anti-T-lymphoglobulin (ATG). The remaining 42 patients received chemotherapy consolidation and maintenance only in first remission. With median follow-up of 18 months, in the URD allo-HSCT group, the relapse rate(RR) was 30.6 ± 11.4 % which was significantly lower than that of the chemotherapy group (80.5 ± 10.1 %,p < 0.001), while non-relapse mortality (NRM) was higher(16.4 ± 6.7 % vs. 0, p = 0.028). Overall, 3-year leukemia free survival (LFS) was superior in the URD allo-HSCT group compared to chemotherapy group (57.8 ± 10.6 vs.19.5 ± 10.5 %, p = 0.002), as was 3-year overall survival(OS, 63.5 ± 13.3 vs. 31.6 ± 10.6 %, p = 0.016). URDHSCT was the only factor associated with improved OS, LFS and reduced RR in multivariate analysis. Based on our data, URD allo-HSCT significantly reduced the relapse in high-risk ALL and the benefit translated into improvement in both LFS and OS. Prospective studies based on availability of HLA-matched URD are warranted to evaluate the precise role of URD transplantation in adult ALL.