This study provides the first evidence of global Treg impairment in IPF that strongly correlates with disease severity, suggesting a role for Tregs in the fibrotic process.

CD4 þ CD25 þ FOXP3 þ T regulatory cells (T regs ) prevent autoimmunity by restricting overexuberant immune responses, but the same subpopulation can incur detrimental effects on antitumor responses. In both cases, the suppressor potential of T regs appears to be strongly influenced by their compartmentalization. In myelodysplastic syndromes (MDS), immune deregulation and autoimmunity in the early stages might lead to ineffective hematopoiesis and bone marrow (BM) failure, whereas late-stage disease is characterized by the immune escape of the malignant clone. We show that these two stages of MDS are associated with differential T reg activity. Specifically, we found that in early stage MDS, compared with normal hematopoiesis and late stage MDS, T regs are dysfunctional and their BM homing through the CXCL12/CXCR4 axis is seriously impaired as a result of CXCR4 downregulation. Conversely, in late stage MDS, T regs are systemically and locally expanded and retain their function and migratory capacity. Moreover, T reg levels follow the disease course and are significantly reduced in treatment responding patients. Our findings indicate T reg involvement in the pathophysiology of MDS; defective suppressor function and BM trafficking of T regs may be important in the autoimmune process of early MDS, but increased T reg activity could favor leukemic clone progression in late stage disease.

This retrospective study aimed to describe the Hellenic experience on the use of brentuximab vedotin (BV) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) given within its indication. From June 2011 to April 2015, ninety‐five patients with R/R HL, who received BV in 20 centers from Greece, were analyzed. Their median age was 33 years, and 62% were males. Sixty‐seven patients received BV after autologous stem cell transplantation failure, whereas 28 patients were treated with BV without a prior autologous stem cell transplantation, due to advanced age/comorbidities or chemorefractory disease. The median number of prior treatments was 4 and 44% of the patients were refractory to their most recent therapy. The median number of BV cycles was 8 (range, 2‐16), and the median time to best response was the fourth cycle. Fifty‐seven patients achieved an objective response: twenty‐two (23%), a complete response (CR), and 35 patients (37%), a partial, for an overall response rate of 60%. Twelve patients (13%) had stable disease, and the remaining twenty‐six (27%) had progressive disease as their best response. At a median follow‐up of 11.5 months, median progression‐free survival and overall survival were 8 and 26.5 months, respectively. Multivariate analysis showed that chemosensitivity to treatment administered before BV was associated with a significantly increased probability of achieving response to BV (P = .005). Bulky disease (P = .01) and response to BV (P <.001) were significant for progression‐free survival, while refractoriness to most recent treatment (P = .04), bulky disease (P = .005), and B‐symptoms (P = .001) were unfavorable factors for overall survival. Among the 22 CRs, 5 remain in CR with no further treatment after BV at a median follow‐up of 13 months. In conclusion, our data indicate that BV is an effective treatment for R/R HL patients even outside clinical trials. Whether BV can cure a fraction of patients remains to be seen.

BackgroundSchizophrenia is associated with structural and functional abnormalities of the hippocampus, which have been suggested to play an important role in the formation and emergence of schizophrenia syndrome. Patients with schizophrenia exhibit significant bilateral hippocampal volume reduction and progressive hippocampal volume decrease in first-episode patients with schizophrenia has been shown in many neuroimaging studies. Dysfunction of the neurotrophic system has been implicated in the pathophysiology of schizophrenia. The initiation of antipsychotic medication alters the levels of serum Brain Derived Neurotrophic Factor (BDNF) levels. However it is unclear whether treatment with antipsychotics is associated with alterations of hippocampal volume and BDNF levels.MethodsIn the present longitudinal study we investigated the association between serum BDNF levels and hippocampal volumes in a sample of fourteen first-episode drug-naïve patients with schizophrenia (FEP). MRI scans, BDNF and clinical measurements were performed twice: at baseline before the initiation of antipsychotic treatment and 8 months later, while the patients were receiving monotherapy with second generation antipsychotics (SGAs).ResultsWe found that left hippocampal volume was decreased (corrected left HV [t = 2.977, df = 13, p = .011] at follow-up; We also found that the higher the BDNF levels change the higher were the differences of corrected left hippocampus after 8 months of treatment with atypical antipsychotics (Pearson r = 0.597, p = 0.024).ConclusionsThe association of BDNF with hippocampal volume alterations in schizophrenia merits further investigation and replication in larger longitudinal studies.

The circulating levels of several angiogenic cytokines [angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2), vascular endothelial growth factor (VEGF), angiogenin and basic fibroblast growth factor (bFGF)] were evaluated in 174 consecutive patients with newly diagnosed, symptomatic, multiple myeloma (MM). Circulating levels of Ang‐1/Ang‐2 were reduced in myeloma patients compared to controls, whereas VEGF and angiogenin levels were increased. Reduced angiopoietin‐1/angiopoietin‐2 ratio correlated with advanced disease features including international staging system (ISS)‐3 stage, renal impairment and extensive bone disease. Based on immunohistochemical results in 20 patients (10 with the higher and 10 with the lower values of circulating angiopoietin‐2) we found that angiopoietin‐2 is expressed by myeloma cells and correlates with increased microvessel density in subsets of patients. Furthermore, Ang‐1/Ang‐2 ratio correlated with survival. Patients with circulating Ang‐1/Ang‐2 below or equal to the median value (6.03) had a median survival of 26.3 months compared to 53 months of all others (p = 0.002). Interestingly, this was mainly observed in patients who received first‐line therapy with novel agent‐based regimens (65% of our patients). Furthermore, a subset of ISS‐3 patients with serum Ang‐1/Ang‐2 above the median value had favourable prognosis (median survival: 45 months versus 17 months of all others; p = 0.0001). The multivariate analysis revealed that low Ang‐1/Ang‐2 ratio could independently predict for inferior survival in our cohort of patients (relative risk (RR) 2.07, 95% CI 1.50–2.42; p < 0.001). These results highlight the role of angiopoietins pathway in the biology of MM and reveal novel targets for the development of antimyeloma agents.