Response to pretransplant hypomethylating agents influences the outcome of allogeneic hematopoietic stem cell transplantation in adults with myelodysplastic syndromes

This study describes a retrospective analysis on the transplant outcome of 56 consecutive patients with myelodysplastic syndrome (MDS) according to their response to hypomethylating agents (HMA). While 2‐yr disease‐free survival (DFS) of patients who transformed to acute myeloid leukemia (n = 12) was 25%, that of the remaining patients with MDS according to response to HMA was 73.1%, 68.1%, 50.0%, and 20.8% in G‐COR (group of continuous response, n = 19), G‐NoC (group of no change, n = 15), G‐LOR (group of loss of response, n = 6), and G‐DP (group of disease progression, n = 4), respectively. When dichotomized as G‐COR/G‐NoC versus G‐LOR/G‐DP, significantly different 2‐yr DFS (71.0% vs. 33.3%; P = 0.004) and relapse (14.1% vs. 46.7%; P = 0.016) were demonstrated. On multivariate analysis, G‐LOR/G‐DP [hazard ratio (HR), 3.91; P = 0.008] and poor karyotype at transplantation (HR, 2.69; P = 0.017) were the significant predictors for poor DFS, as G‐LOR/G‐DP was for relapse (HR, 6.28; P = 0.011). DFS was significantly poor in patients with any of the two predictors in all MDS (81.5% vs. 34.9%; P = 0.001) or higher‐risk MDS (HrMDS) at the time of HMA (80.7% vs. 29.2%; P = 0.005). G‐COR showed a trend of better DFS compared with G‐NoC among HrMDS (74.6% vs. 36.5%; P = 0.090). These results implicate the significance of response to HMA on hematopoietic stem cell transplantation (HSCT) outcomes and support the need for future study to verify the suggested strategy of proceeding to transplantation before LOR or DP, especially for HrMDS.     

Surgical Outcomes of Canalicular Trephination Combined with Endoscopic Dacryocystorhinostomy in Patients with Distal or Common Canalicular Obstruction

PurposeThis study investigated the surgical outcomes of canalicular trephination combined with endoscopic dacryocystorhinostomy (DCR) in patients with a distal or common canalicular obstruction. It also identified the factors affecting surgical success rates associated with this technique.MethodsWe retrospectively reviewed the medical records of 57 patients (59 eyes) in whom a canalicular obstruction was encountered during endoscopic DCR. All patients were treated with endoscopic DCR, followed by canalicular trephination and silicone tube placement. The surgical outcome was categorized as a functional success according to the patient''s subjective assessment of symptoms, including epiphora, and as an anatomical success according to a postoperative nasolacrimal duct irrigation test. Surgical success rates were compared based on age, sex, location of the obstruction, number of silicone tubes, and experience of the surgeon.ResultsFunctional success was achieved in 55 of 59 eyes (93%) at one month, 50 eyes (84%) at three months, and 46 eyes (78%) at six months. Anatomical success was achieved in 58 of 59 eyes (98%) at one month, 52 eyes (88%) at three months, and 50 eyes (84%) at six months. There was a statistically significant difference in surgical outcome according to the experience of the surgeon. The anatomical success rate at the six-month follow-up exam was 95.4% in the >5 years of experience group, and 53.3% in the <5 years of experience group (p = 0.008, Pearson chi-square test).ConclusionsThe success rate of canalicular trephination combined with endoscopic DCR in patients with a distal or common canalicular obstruction decreased gradually during the six-month follow-up period. In particular, patients undergoing procedures with experienced surgeons tended to show excellent surgical outcomes at the six-month follow-up exam.     

Effect of PRX-1 Downregulation in the Type 1 Diabetes Microenvironment

Type 1 diabetes (T1D) is caused by dysregulation of the immune system in the pancreatic islets, which eventually leads to insulin-producing pancreatic β-cell death and destabilization of glucose homeostasis. One of the major characteristics of T1D pathogenesis is the production of inflammatory mediators by macrophages that result in destruction or damage of pancreatic β-cells. In this study the inflammatory microenvironment of T1D was simulated with RAW264.7 cells and MIN6 cells, acting as macrophages and pancreatic β-cells respectably. In this setting, peroxiredoxin-1, an anti-oxidant enzyme was knocked down to observe its functions in the pathogenesis of T1D. RAW264.7 cells were primed with lipopolysaccharide and co-cultured with MIN6 cells while PRX-1 was knocked down in one or both cell types. Our results suggest that hindrance of PRX-1 activity or the deficiency of this enzyme in inflammatory conditions negatively affects pancreatic β-cell survival. The observed decrease in viability of MIN6 cells seems to be caused by nitric oxide production. Additionally, it seems that PRX-1 affects previously reported protective activity of IL-6 in pancreatic β cells as well. These results signify new, undiscovered roles for PRX-1 in inflammatory conditions and may contribute toward our understanding of autoimmunity.     

Role of metabolism by intestinal microbiota in pharmacokinetics of oral baicalin

Baicalin (baicalein-7-glucuronide) is a flavonoid purified from Scutellaria baicalensis Georgi that has traditionally been used for treatment of hypertension, cardiovascular diseases, and viral hepatitis. In this study, the effects of intestinal microbiota on the pharmacokinetics of baicalin were investigated in normal and antibiotic-pretreated rats following p.o. administration of 100 mg/kg baicalin by using liquid chromatography/ion trap mass spectrometry. When rats were pretreated orally with cefadroxil, oxytetracycline and erythromycin for 3 days to control the number of intestinal bacteria, the pharmacokinetic parameters of oral baicalin were significantly affected by antibiotics: C_max, T_1/2(β), K_el and AUC values were significantly changed compared to those in normal rats. These results indicate that intestinal microbiota might play a key role in the oral pharmacokinetics of baicalin.