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Purpose To identify risk factors, including FRAX (a tool for assessing osteoporosis) scores, for development of proximal junctional kyphosis (PJK), defined as Type 2 in the Yagi–Boachie classification (bone failure), with vertebral fracture (VF) after surgery for symptomatic adult spinal deformity. Methods This was a retrospective, single institution study of 127 adults who had undergone corrective long spinal fusion of six or more spinal segments for spinal deformity and been followed up for at least 2 years. The main outcome was postoperative development of PJK with VF. Possible predictors of this outcome studied included age at surgery, BMI, selected radiographic measurements, bone mineral density, and 10-year probability of major osteoporotic fracture (MOF) as determined by FRAX. We also analyzed use of medications for osteoporosis. Associations between the selected variables and PJK with VF were assessed by the Mann–Whitney, Fishers exact, and Wilcoxon signed-rank tests, and Kaplan–Meier analysis, as indicated. Results Forty patients (31.5%) developed PJK with VF postoperatively,73% of them within 6 months of surgery. Statistical analysis of the selected variables found that only a preoperative estimate by FRAX of a > 15% risk of MOF within 10 years, pelvic tilt > 30° at first standing postoperatively and lower instrumented level (fusion terminating at the pelvis) were significantly associated with development of PJK with VF. Conclusion Preoperative assessment of severity of osteoporosis using FRAX provides an accurate estimate of risk of postoperative PJK with VF after surgery for adult spinal deformity.

This study aimed to investigate the prognostic relevance of cytogenetic risk in 9826 adults with acute myeloid leukemia (AML) who underwent allogeneic hematopoietic cell transplantation (HCT) during the first or second complete remission. The 5-year probabilities of overall survival (OS) were 66%, 61%, and 47% (P < 0.001), the cumulative incidences of relapse were 14%, 19%, and 32% (P < 0.001), and the cumulative incidences of non-relapse mortality (NRM) were 23%, 23%, and 25% (P = 0.208) in patients with favorable (n = 1418), intermediate (n = 6747), and poor cytogenetic risk (n = 1661), respectively. The significant effect of cytogenetic risk on OS was strong in all subgroups stratified by age, sex, performance status, disease status, donor type, conditioning intensity, graft-versus-host disease prophylaxis, and transplantation period (P < 0.001 for all). The evaluation of trends in posttransplant outcomes for patients in each cytogenetic risk category indicated that the risk of relapse declined in patients with favorable and intermediate cytogenetics and that the risk of NRM decreased in those with intermediate and poor cytogenetics. Therefore, patients with intermediate cytogenetics experienced the best OS improvement. These results confirm cytogenetic risk as a universal prognostic factor in patients with AML undergoing allogeneic HCT while highlighting the requirement for further improvements in posttransplant OS by reducing NRM in patients with favorable cytogenetics and by reducing relapse in patients with poor cytogenetics.

An 11q23 abnormality presents in approximately 5% of adults with acute myeloid leukemia (AML) and is associated with adverse outcomes even after allogeneic hematopoietic cell transplantation (allo-HCT). To evaluate the outcomes and prognostic factors following allo-HCT for adult AML with 11q23 abnormality, we retrospectively analyzed the Japanese registration data of 322 adult AML patients with 11q23 abnormality who had received allo-HCT between 1990 and 2014. In total, the disease status at HCT was first complete remission (CR1) in 159 (49%) patients. The probability of overall survival and the cumulative incidence of relapse at 3 years were 44 and 44%, respectively. In the multivariate analysis, disease status beyond CR1 at the time of HCT was significantly associated with a higher overall mortality and relapse. The 11q23 fusion partner did not have a significant impact on survival. We also evaluated the prognostic value of minimal residual disease (MRD) status at HCT on transplant outcomes among hematological CR patients. MRD status at HCT was the significant prognostic indicator for hematological relapse and survival. These data suggested that allo-HCT offered a curative option for adult AML with 11q23 abnormality. Pretransplant MRD status was the significant prognostic indicator for relapse and survival in CR patients.

Ubiquitin-like with PHD and RING finger domain-containing protein 1 (UHRF1)-dependent DNA methylation is essential for maintaining cell fate during cell proliferation. Developmental pluripotency-associated 3 (DPPA3) is an intrinsically disordered protein that specifically interacts with UHRF1 and promotes passive DNA demethylation by inhibiting UHRF1 chromatin localization. However, the molecular basis of how DPPA3 interacts with and inhibits UHRF1 remains unclear. We aimed to determine the structure of the mouse UHRF1 plant homeodomain (PHD) complexed with DPPA3 using nuclear magnetic resonance. Induced α-helices in DPPA3 upon binding of UHRF1 PHD contribute to stable complex formation with multifaceted interactions, unlike canonical ligand proteins of the PHD domain. Mutations in the binding interface and unfolding of the DPPA3 helical structure inhibited binding to UHRF1 and its chromatin localization. Our results provide structural insights into the mechanism and specificity underlying the inhibition of UHRF1 by DPPA3. Competing Interest Statement The authors have declared no competing interest. Footnotes * Some experiments were performed according to reviewer's suggestions. DNA methylation analysis in Xenopus egg extracts/mESC, NMR experiments and in vitro ubiquitination assay results have been added in the revised manuscript.