No abstract

We studied acute myeloid leukemia (AML) patients with lympho-myeloid clonal hematopoiesis (LM-CH), defined by the presence of DNA methyltransferase 3A (DNMT3A) mutations in both the myeloid and lymphoid T-cell compartment. Diagnostic, complete remission (CR) and relapse samples were sequenced for 34 leukemia-related genes in 171 DNMT3A mutated adult AML patients. AML with LM-CH was found in 40 patients (23%) and was associated with clonal hematopoiesis of indeterminate potential years before AML, older age, secondary AML and more frequent MDS-type co-mutations (TET2, RUNX1 and EZH2). In 82% of AML patients with LM-CH, the preleukemic clone was refractory to chemotherapy and was the founding clone for relapse. Both LM-CH and non-LM-CH MRD-positive AML patients who achieved CR had a high risk of relapse after 10 years (75% and 75%, respectively) compared with patients without clonal hematopoiesis in CR with negative MRD (27% relapse rate). Long-term survival of patients with LM-CH was only seen after allogeneic hematopoietic stem cell transplantation (HSCT). We define AML patients with LM-CH as a distinct high-risk group of AML patients that can be identified at diagnosis through mutation analysis in T cells and should be considered for HSCT.

Counselling on sports activities following joint replacement needs to consider individual motives, barriers and previous sports experience in order to be perceived as supportive.

Internationally, there is debate on the safety of different birth settings inside and outside of hospitals. Low-risk women in Germany can choose where they give birth, and out-of-hospital births are especially necessary in regions lacking infrastructure. To date, national studies are required. We investigated planned out-of-hospital (OH) and hospital births in Lower Saxony, Germany, in 2005. Women with a singleton fetus in the vertex position were included once they reached 34+0 gestational weeks. 1 273 out of 4 424 births were included via risk assessment. Outcomes were compared using Pearson's chi-squared test, the Mann-Whitney test, and logistic regression. 152 (36.6%) nulliparae (NP) and 263 (63.4%) multiparae (MP) gave birth out of hospital, 439 (51.2%) nulliparae and 419 (48.8%) multiparae in a hospital. 10.1% of women whose care started outside of the hospital needed a transfer to the hospital. Women who planned OH were older and had a higher level of education. Women without a migration background displayed an increased rate of out-of-hospital birth. A higher proportion received their antenatal care from midwives rather than medical doctors. Induction of labor was less likely for women with planned out-of-hospital births, as were other intrapartum interventions. In hospital births, fetal monitoring was more likely performed via cardiotocograph instead of intermittent auscultation. Duration of labor was significantly longer in OH births (median: NP: 9.01 h vs. 7.38 h; MP: 4.53 h vs. 4.25 h). Nulliparae had more spontaneous births out-of-hospital (94.7%) than in hospital (73.6%). There was no difference in adverse fetal outcomes, blood loss, and severe perineal lacerations. The perineum was less frequently intact in hospital births. Retained placenta was more often documented in out-of-hospital births. In an out-of-hospital setting, fewer interventions were performed, spontaneous births occurred more often, and there was no difference in neonatal outcomes. OH birth appears reasonably safe with thorough pre-labor risk assessment and good transfer management. Some beneficial aspects of OH birth care (like continuity of care and restriction of routine interventions) could be adopted by hospital labor wards, leading to a higher rate of vaginal births and improved care.