The long-term viscoelastic material properties of monkey peripapillary sclera are altered by exposure to moderate, short-term, chronic IOP elevations and these alterations are present at the onset of CSLT-detected glaucomatous damage to the ONH. Damage to and/or remodeling of the extracellular matrix of these tissues may underlie these changes in scleral material properties.

We evaluated the feasibility of T-cell-depleted haploidentical hematopoietic SCT (HHCT) in pediatric patients. Between July 2008 and January 2013, 28 patients underwent ex vivo T-cell-depleted HHCT; 9 had hematologic malignancy, 18 had nonmalignant hematologic disease, and 1 had refractory neuroblastoma. Twenty-six patients achieved neutrophil engraftment at a median of 11 days (range, 9-15 days). Two patients failed to achieve primary engraftment and five experienced graft rejection after primary engraftment. These seven patients achieved stable engraftment after a second HHCT. The cumulative incidences (CIs) of ⩾ grade II and ⩾ grade III acute GVHD were 33.3% and 14.3%, respectively, and the 1-year CI of extensive chronic GVHD was 11.1%. Four patients died of non-relapse-related causes (two of CMV disease, one of encephalopathy and one of autoimmune hemolytic anemia) and one of leukemia relapse. Non-relapse mortality at 100 days, 1 year and 2 years was 0.0%, 10.7% and 14.3%, respectively. At a median follow-up of 32.8 months (range, 17.0-72.5 months), the 2-year OS was 82.1%. OSs for nonmalignant diseases and malignant diseases were 94.4% and 60.0%, respectively (P = 0.019). Thus, HHCT is a realistic alternative for patients with malignant or nonmalignant diseases who lack a suitable donor.Bone Marrow Transplantation (2015) 50, 225-231; doi:10.1038/bmt.2014.232; published online 13 October 2014 INTRODUCTION Recent advances in haploidentical hematopoietic SCT (HHCT) have improved outcomes and enabled the use of haploidentical relatives as donors for children and adults with diseases that are curable with hematopoietic cell transplantation (HCT).A recently developed transplant strategy using a CD3/CD19-depleted graft instead of CD34 + cell selection has shown improved results. [1][2][3] Depleting CD3 + cells is superior to selecting CD34 + cells in terms of rapid engraftment and immune reconstitution. 2,3 Depletion of CD3 + T cells also has the advantage of increasing the number of natural killer cells, monocytes and other immunomodulating cells. 4 We recently completed our prospective study of in vitro CD3-depleted HHCT for pediatric patients lacking suitable related or unrelated donors. We reported our experience with CD3-depleted HHCT for patients with acquired SAA and patients with graft failure (GF) after allogeneic HCT. 5,6 These patients constitute part of the current patient cohort: of 28 patients in the present cohort, 17 were included in the previous two reports. The purpose of the present study was to assess the efficacy and feasibility of CD3-depleted HHCT in the children and adolescents of our cohort with an additional 11 patients and with an extended follow-up of previously reported cases.

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Between 2012 and 2015, 42 pediatric patients underwent haploidentical hematopoietic cell transplantation using an αβ + T-cell-depleted graft with targeted αβ cells at 1-5 × 10 5 /kg by add-back; 31 had hematologic malignancy (HM), 8 had non-malignant disease (NM) and 3 had solid tumors. All patients received uniform reduced-intensity conditioning with fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin and low-dose TBI. All 42 patients achieved neutrophil engraftment at a median of 10 days. The cumulative incidences (CIs) of ⩾ grade II and ⩾ grade III acute GvHD were 31 ± 7.1% (SE) and 12 ± 5.0%, respectively, and 1-year CI of chronic GvHD was 15 ± 5.8%. One patient died of CMV pneumonia, leading to transplant-related mortality (TRM) of 2.6 ± 2.5%. Sixteen patients relapsed and 11 died of disease. At a median follow-up of 19 months (range, 5-43 months), the estimated 2-year event-free survival for NM and HM were 88 ± 11.7 and 50 ± 10.1%, respectively. Our study demonstrated that haploidentical hematopoietic cell transplantation after ex vivo depletion of αβ + T cells with targeted dose noticeably reduced the graft failure rate and TRM in pediatric patients and could be applied to patients lacking a suitable related or unrelated donor. While αβ + T cells are known to be associated with the initiation of GvHD, γδ + T cells can enhance immune reconstitution and are not implicated in GvHD. 6 Recently, we reported our experience with HHCT using a CD3-depleted graft. 7 Since 2012, we have initiated HHCT using ex vivo depletion of αβ + T cells with targeted αβ cells at 1-5 × 10 5 /kg after add-back. Here, we report our prospective results using αβ-depleted grafts in HHCT for children and adolescents with malignant or non-malignant disease.

Objectives: Inhibitors of the renin-angiotensin system, namely, angiotensinconverting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), and HMG-CoA reductase inhibitors, statins, have been reported to have anti-inflammatory effects. This study is to assess the association of ACEI, ARB, and statin with sepsis-related outcomes. MethOds: A retrospective cohort study was conducted using the Health Insurance Review and Assessment Service (HIRA) claims data. In adult patients hospitalized with sepsis in 2012, those who took ARB, ACEI, or statin 30 days before admission were identified. The outcomes were in-hospital death and length of stay (LOS) and the logistic regression and generalized linear model were carried out to examine the relation between the prior use of medication and the outcomes. Results: A total of 27,365 sepsis patients were included in the analysis, where the number of patients taking ACEI, ARB, or statin prior to sepsis hospitalization were 1,207 (4.41%), 3,951 (14.44%), and 2,473 (9.04%), respectively. After adjusting for age, sex, characteristics of hospitalization, and comorbidities, prior use of ACEI (Odds Ratio (OR) 0.752, 95% Confidence Interval (CI): 0.661-0.855), ARB (OR 0.575, 95% CI: 0.532-0.621), or statin (OR 0.716, 95% CI: 0.651-0.788) were significantly associated with decreased in-hospital mortality. Although the treatment of ACEI, ARB, or statin before admission were related to increased LOS, prior use of ARB was only associated with increased LOS after excluding death cases (OR 1.24, 95% CI: 1.16-1.32). cOnclusiOns: Use of ACEI, ARB, or statin before hospitalization appeared to be associated with decreased mortality in sepsis patients. Further prospective randomized control trials are needed to evaluate the beneficial effect of ACEI, ARB, and statin in sepsis.

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