Pre-existing osteoporosis and serum vitamin D levels in patients with distal radius fractures: are we missing something?

INTRODUCTION: Given the significant therapeutic gap for osteoporosis, this study aims to investigate the most common osteoporosis-related fracture. The analysis will also consider patients' serum vitamin D levels and the indications for basic osteoporosis diagnostic tests and osteoporosis therapy prior to fracture. MATERIALS AND METHODS: This prospective clinical trial included patients with distal radius fractures who underwent surgery at our hospital between 1 April 2021 and 7 April 2022. Blood samples were taken from all participants and existing risk factors for osteoporosis were recorded. In addition, the indication for a guideline-based osteoporosis diagnosis was assessed and the risk of another future fracture with FRAX® was calculated. This information was used to decide whether there was an indication for specific osteoporosis therapy. RESULTS: A diagnosis gap of 53% and a treatment gap of 84% were identified among the 102 patients investigated. The patients' ages ranged from 46 to 91 years, with an average vitamin D level of 57 nmol/l, which was below the recommended level of 75 nmol/l. It was noted on a monthly basis that the vitamin D level (without substitution) never exceeded the recommended value of 75 nmol/l in any month. Three-quarters of patients had indications for a baseline osteoporosis diagnosis, yet less than 50% received one. According to FRAX® data, 57% of patients had indications for specific osteoporosis treatment before experiencing the fracture. CONCLUSION: Even without a previous distal radius fracture, many patients are in need of osteoporosis diagnosis or treatment. Our research suggests that patients with distal radius fractures should have their vitamin D levels checked via a blood test and be evaluated for osteoporosis. As endogenous vitamin D levels are often inadequate, year-round vitamin D supplementation should be considered for the prevention of osteomalacia and as a basis for the treatment of osteoporosis. GERMAN CLINICAL TRIAL REGISTER ID: DRKS00028085.

Real-world experience of CPX-351 as first-line treatment for patients with acute myeloid leukemia.

To investigate the efficacy and toxicities of CPX-351 outside a clinical trial, we analyzed 188 patients (median age 65 years, range 26-80) treated for therapy-related acute myeloid leukemia (t-AML, 29%) or AML with myelodysplasia-related changes (AML-MRC, 70%). Eighty-six percent received one, 14% two induction cycles, and 10% received consolidation (representing 22% of patients with CR/CRi) with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10-3) as measured by flow cytometry. After a median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate 64%. In multivariate analysis, complex karyotype predicted lower response (p = 0.0001), while pretreatment with hypomethylating agents (p = 0.02) and adverse European LeukemiaNet 2017 genetic risk (p < 0.0001) were associated with lower OS. Allogeneic hematopoietic cell transplantation (allo-HCT) was performed in 116 patients (62%) resulting in promising outcome (median survival not reached, 1-year OS 73%), especially in MRD-negative patients (p = 0.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings. These real-world data confirm CPX-351 as efficient treatment for these high-risk AML patients facilitating allo-HCT in many patients with promising outcome after transplantation.

In vivo assembly of DNA-fragments in the moss, Physcomitrella patens.

Direct assembly of multiple linear DNA fragments via homologous recombination, a phenomenon known as in vivo assembly or transformation associated recombination, is used in biotechnology to assemble DNA constructs ranging in size from a few kilobases to full synthetic microbial genomes. It has also enabled the complete replacement of eukaryotic chromosomes with heterologous DNA. The moss Physcomitrella patens, a non-vascular and spore producing land plant (Bryophyte), has a well-established capacity for homologous recombination. Here, we demonstrate the in vivo assembly of multiple DNA fragments in P. patens with three examples of effective genome editing: we (i) efficiently deleted a genomic locus for diterpenoid metabolism yielding a biosynthetic knockout, (ii) introduced a salt inducible promoter, and (iii) re-routed endogenous metabolism into the formation of amorphadiene, a precursor of high-value therapeutics. These proof-of-principle experiments pave the way for more complex and increasingly flexible approaches for large-scale metabolic engineering in plant biotechnology.