PurposeGenexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol).Materials and MethodsPatients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 intravenously every 3 weeks. The primary outcome was the objective response rate (ORR).ResultsThe study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m2 (95.0%), and that of Genexol was 168.3±10.6 mg/m2 (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (pnon-inferiority=0.021, psuperiority=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments.ConclusionCompared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB ( n = 28), and followed by ANK1 ( n = 19), SLC4A1 ( n = 3), SPTA1 ( n = 2), EPB41 ( n = 1), and EPB42 ( n = 1). Concurrent mutations of genes encoding RBC enzymes ( ALDOB, GAPDH, and GSR ) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS. Electronic supplementary material The online version of this article (10.1186/s13023-019-1070-0) contains supplementary material, which is available to authorized users.

We achieved highly enantioselective synthesis of cyclic 1,2-sulfamidates and -sulfamides via rhodium-catalyzed transfer hydrogenation, and also revealed one-pot preparation of cyclic N-sulfonylimines from α-hydroxy ketones.

Objective This study aims to identify distinct patterns of 10-year multimorbidity trajectory among Korean older adults and examine factors associated with the patterns. Methods Data were drawn from the six waves of the Korean Longitudinal Study of Ageing (KLoSA, 2006–2016). We examined trajectories of multimorbidity of 1,705 older adults aged 65 and older using Growth Mixture Modeling. Then, the identified patterns were used as dependent variables to examine the correlates of multimorbidity trajectories. Explanatory variables considered were sociodemographic, psychological, health behavioural and interpersonal factors at baseline. Results Four distinct patterns of multimorbidity trajectories were identified: ‘maintaining-low’ (59.4%), ‘chronically-high’ (7.5%), ‘moderately-increasing’ (26.0%) and ‘rapidly- increasing’ (7.1%). Gender, depressive symptoms, life satisfaction and frequency of contacts with others were associated with trajectory membership. Specifically, women were more likely to be in the ‘chronically-high’ group than any other groups. Compared to the ‘maintaining-low’ group, those with higher levels of depressive symptoms and lower levels of life satisfaction were more likely to belong to the ‘chronically-high’ group and ‘moderately-increasing’ group, respectively. Respondents who had less frequent meetings with others in close relationships were more likely to be in the ‘rapidly-increasing’ group than the ‘maintaining-low’ group. Discussion These findings are suggestive of distinct trajectories of multimorbidity across older adulthood, indicating that multimorbidity experiences might differ among older adults. Moreover, results suggest that there may be gender inequalities in multimorbidity trajectories, and that levels of psychological well-being and social engagement could be useful in identifying older adults who are at higher risk of worsening multimorbidity.

Background: The use of a functionally closed system for the glycerolization and deglycerolization of red blood cells (RBCs) allows for prolonged post-thaw storage for more than 24 hours. The aim of this study was to assess glycerolization and deglycerolization processing for RBCs using a high glycerol method in the automated, closed system provided by Haemonetics ACP 215. Methods: Thirty-five packed RBCs were glycerolized using the ACP 215 to a final concentration of 40% (wt/vol). The units were either frozen as such (n=30) or excess glycerol was removed (n=5) before freezing. After storage at-80 o C, the units were thawed, deglycerolized and resuspended in SAG-M. The frozen-thawed RBCs were stored at 4 o C, and analyzed for their stability and in vitro quality. Results: No prefreeze excess glycerol removal units showed significantly less potassium leakage during post-thaw storage compared to the prefreeze excess glycerol removal units. All measurements of the stability and in vitro quality of thawed RBCs prepared from frozen RBCs without the prefreeze removal of excess glycerol during post-thaw storage at 4 o C for 7 days were acceptable to the American Blood Bank Association's standards and European standards. Conclusion: RBCs frozen without prefreeze removal of excess glycerol and the ACP 215 simplifies cryopreservation procedure and increases the stability of frozen-thawed RBCs. This increases the practical applicability of cryopreserved RBCs in blood transfusion practice.