Despite an increasing focus on transdiagnostic approaches to mental health, it remains unclear whether different diagnostic categories share a common neuronatomical basis. The current investigation sought to investigate whether a transdiagnostic set of structural alterations characterized schizophrenia, depression, post-traumatic stress disorder, and obsessive-compulsive disorder, and determine whether any such alterations reflected markers of psychiatric illness or pre-existing familial vulnerability. A total of 404 patients with a psychiatric diagnosis were recruited (psychosis, n = 129; unipolar depression, n = 92; post-traumatic stress disorder, n = 91; obsessive-compulsive disorder, n = 92) alongside n = 201 healthy controls and n = 20 unaffected first-degree relatives. We collected structural magnetic resonance imaging scans from each participant, and tested for transdiagnostic alterations using Voxel-based morphometry. Inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. The four psychiatric groups relative to healthy controls were all characterized by significantly greater gray matter volume in the putamen (right: z-score: 5.97, p-value < 0.001; left: z-score: 4.97, p-value = 0.001); the volume of this region was positively correlated with severity of symptoms across groups (r = 0.313; p < 0.001). Putamen enlargement was also evident in unaffected relatives compared to healthy controls (right: z-score: 8.13, p-value < 0.001; left: z-score: 9.38, p-value < 0.001). Taken collectively, these findings indicate that increased putamen volume may reflect a transdiagnostic marker of familial vulnerability to psychopathology. This is consistent with emerging conceptualizations of psychiatric illness, in which each disorder is understood as a combination of diagnosis-specific features and a transdiagnostic factor reflecting general psychopathology.

BackgroundRituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP). However, its role in the management of pediatric ITP requires clarification. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of rituximab for children with ITP.Methodology/Principal FindingsWe searched MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, abstract databases of American Society of Hematology, American Society of Clinical Oncology and Pediatric Academic Society. Clinical studies published in full text or abstract only in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Safety was evaluated from all studies that reported data of toxicity. 14 studies (323 patients) were included for efficacy assessment in children with primary ITP. The pooled complete response (platelet count ≥100×109/L) and response (platelet count ≥30×109/L) rate after rituximab treatment were 39% (95% CI, 30% to 49%) and 68% (95%CI, 58% to 77%), respectively, with median response duration of 12.8 month. 4 studies (29 patients) were included for efficacy assessment in children with secondary ITP. 11 (64.7%) of 17 patients associated with Evans syndrome achieved response. All 6 patients with systemic lupus erythematosus associated ITP and all 6 patients with autoimmune lymphoproliferative syndrome associated ITP achieved response. 91 patients experienced 108 adverse events associated with rituximab, among that, 91 (84.3%) were mild to moderate, and no death was reported.Conclusions/SignificanceRandomized controlled studies on effect of rituximab for children with ITP are urgently needed, although a series of uncontrolled studies found that rituximab resulted in a good platelet count response both in children with primary and children secondary ITP. Most adverse events associated with rituximab were mild to moderate, and no death was reported.

. Combination of common and novel rare NUDT15 variants improves predictive sensitivity of thiopurine-induced leukopenia in children with acute lymphoblastic leukemia.

PurposeIn absence of direct comparison randomized controlled trials (RCTs), indirect comparison was conducted to evaluate the efficacy and safety of thrombopoietin-receptor agonists (TPO-RAs) in treatment of adult immune thrombocytopenia (ITP).MethodsWe searched PubMed, Embase and Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database from their earliest records to May 2017. RCTs comparing the TPO-RAs with placebo in adult ITP were included. Primary outcomes were the overall response rate. Secondary outcomes included safety, durable response, overall or clinically significant bleeding, and the proportion of patients receiving rescue medication.ResultsNine randomized placebo-controlled trials (786 participants) were included in this systematic review. Overall response [Risk Ratio(RR) = 0.59, 95%Confidence Interval(CI): 0.24–1.45], the incidence of adverse events (RR = 0.98, 95%CI: 0.79–1.21), durable response (RR = 0.47, 95%CI: 0.08–2.81), the incidence of overall bleeding (RR = 1.15, 95%CI: 0.52–2.57) and clinically significant bleeding (RR = 1.09, 95%CI: 0.37–3.24), and the proportion of patients receiving rescue treatment (RR = 0.95, 95%CI: 0.47–1.90) were similar between eltrombopag and romiplostim.ConclusionsEltrombopag and romiplostim might be equivalent in efficacy and safety for adult ITP, however, physicians should still take into account drug cost and comorbidities of the specific patient while making decisions on the treatment of ITP with TPO-RAs.RegistrationPROSPERO International Prospective Register of Systematic Review (PROSPERO 2017: CRD42017068661).

The goals of the current study were to determine whether topological organization of brain structural networks is altered in youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63). Brain networks were constructed based on the similarity of morphological features across regions and analyzed using graph theory approaches. We tested for pretreatment anatomical differences between bipolar and healthy youth and for changes in neuroanatomic network metrics following treatment in the youth with bipolar disorder. Youth with bipolar disorder showed significantly increased clustering coefficient (Cp) (p = 0.009) and characteristic path length (Lp) (p = 0.04) at baseline, and altered nodal centralities in insula, inferior frontal gyrus, and supplementary motor area. Cp, Lp, and nodal centrality of the insula exhibited normalization in patients following treatment. Changes in these neuroanatomic parameters were correlated with improvement in manic symptoms but did not differ between the two drug therapies. Baseline structural network matrices significantly differentiated medication responders and non-responders with 80% accuracy. These findings demonstrate that both global and nodal structural network features are altered in early course bipolar disorder, and that pretreatment alterations in neuroanatomic features predicted treatment outcome and were reduced by treatment. Similar connectome normalization with lithium and quetiapine suggests that the connectome changes are a downstream effect of both therapies that is related to their clinical efficacy.