Effect of a Patient Blood Management Program on the Appropriateness of Red Blood Cell Transfusion and Clinical Outcomes in Elderly Patients Undergoing Hip Fracture Surgery.

BACKGROUND: Elderly patients with hip fractures frequently receive perioperative transfusions, which are associated with increased morbidity and mortality. This study aimed to evaluate the impact of a patient blood management (PBM) program on the appropriateness of red blood cell (RBC) transfusion and clinical outcomes in geriatric patients undergoing hip fracture surgery. METHODS: In 2018, the revised PBM program was implemented at the Korea University Anam Hospital, Seoul, Republic of Korea. Elderly patients aged ≥ 65 years who underwent hip fracture surgery from 2017 to 2020 were evaluated. Clinical characteristics and outcomes were analyzed according to the timing of PBM implementation (pre-PBM, early-PBM, and late-PBM). Multiveriate regression analysis was used to evaluate the risk factors of the adverse outcomes, such as in-hospital mortality or 30-day readmission. RESULTS: A total of 884 elderly patients were included in this study. The proportion of patients who received perioperative RBC transfusions decreased significantly (43.5%, 40.1%, and 33.2% for pre-PBM, early-PBM, and late-PBM, respectively; P = 0.013). However, the appropriateness of RBC transfusion significantly increased (54.0%, 60.1%, and 94.7%, respectively; P < 0.001). The duration of in-hospital stay and 30-day readmission rates significantly decreased. Multivariable regression analysis revealed that RBC transfusion (odds ratio, 1.815; 95% confidence interval, 1.137-2.899; P = 0.013) was significantly associated with adverse outcomes. CONCLUSION: Implementing the PBM program increased the appropriateness of RBC transfusion without compromising transfusion quality and clinical outcomes. Therefore, adopting the PBM program may improve the clinical management of elderly patients following hip fracture surgery.

Anti-obesity potential of enzymatic fragments of hyaluronan on high-fat diet-induced obesity in C57BL/6 mice.

Hyaluronan has diverse biological activities depending on its molecular size. The hyaluronan fragments (50 kDa) can decrease adipogenic differentiation in vitro. However, in vivo anti-obesitic effects of hyaluronan fragments have not been elucidated. Therefore, we examined the anti-obesity effects of hyaluronan fragments on high-fat diet induced obesity in C57BL/6 mice. Oral administration of hyaluronan fragments (200 mg/kg for 8 weeks) decreased body weight, adipose tissues, serum lipid (low-density lipoprotein cholesterol, triglyceride), and leptin level. Hyaluronan fragments decreased the hypertrophy of adipose tissue and ameliorated liver steatosis. The mRNA expression of leptin was reduced in adipocyte by treatment with hyaluronan fragments. Additionally, hyaluronan fragments enhanced the mRNA expression of PPAR-α and its target genes UCP-2 and decreased mRNA expression of PPAR- γ and fatty acid synthase in liver. In conclusions, hyaluronan fragments had marked effects on inhibiting the development of obesity in obese mice fed the high-fat diet. It suggested that enhancing PPAR-α and suppressing PPAR-γ expression are two possible mechanisms for the anti-obesitic effect of hyaluronan fragments.

Implication of immunokine profiling for cancer staging.

Tumor may arise from the dysregulation of immune system, which plays pivotal roles in counteracting tumor colonization, late-stage tumors, and metastases. In the midst of the establishment of cancer in vivo, immune cells are activated to release a multitude of immunokines, such as cytokines, and chemokines. Thus, since cytokine levels in tumor bearing host would be differential among local (intratumoral lesion, peritumoral normal tissue), and systemic sample site (serum), these differences might be significantly correlated to prognosis and treatment outcome for cancer patients. Previously, despite small number of patients, we demonstrated the feasibility of this proposition via only cytokine profiling. Based on this, herein we propose that immunokine profiling would be used as a surrogate, predictive tool for cancer staging, and progression.

Enzymatic fragments of hyaluronan inhibit adipocyte differentiation in 3T3-L1 pre-adipocytes.

Hyaluronan has diverse biological activities depending on its molecular size. High molecular weight hyaluronan (2000 kDa) is a major component of extracellular matrix, and has been used in wounding healing, extracellular matrix regeneration, and in the treatment of osteoarthritis. Hyaluronan fragments can stimulate inflammation or induce loss of extracellular matrix. Hyaluronan is expressed during adipocyte differentiation, and down regulation of hyaluronan synthesis can reduce adipogenic differentiation. However, the direct effects of hyaluronan fragments on adipocyte differentiation have not been elucidated. Therefore, we prepared hyaluronan fragments by enzymatic digestion, and examined the inhibitory effects of these hyaluronan fragments on the accumulation of lipid droplets and on adipogenic gene mRNA expression in differentiating 3T3-L1 pre-adipocytes. Medium sized hyaluronan fragments (50 kDa) decreased lipid droplet accumulation in a dose-dependent manner. However, high molecular weight hyaluronan did not inhibit lipid droplet accumulation when used at a concentration of 600 µg/ml. Two or 4 day treatments with medium molecular weight of hyaluronan resulted in similar inhibitory levels of lipid accumulation as did treatment for 8 days. Medium sized hyaluronan inhibited the differentiation of 3T3-L1 pre-adipocytes during the early stages of adipogenesis. When 3T3-L1 cells were treated with 180 µg/ml of medium sized hyaluronan, the mRNAs for the master adipogenic transcription factors PPAR-γ and C/EBP-α were inhibited. Additionally, medium molecular weight hyaluronan suppressed mRNA expression of PPAR-γ target genes, including aP2 and FAS. This study is the first to report that medium molecular weight hyaluronan fragments can inhibit adipocyte differentiation.

Synthesis of diethylamino-curcumin mimics with substituted triazolyl groups and their sensitization effect of TRAIL against brain cancer cells.

A newly designed curcumin mimic library (11a-11k) with 2-ethylamino groups in a chalcone structure and variously substituted triazole groups as side chains was synthesized using the Huisgen 1,3-cycloaddition reaction between various alkynes (a-k) and an intermediate (10), with CuSO4 and sodium ascorbate in a solution mixture of chloroform, ethanol, and water (5:3:1) at room temperature for 5h. In the lactate dehydrogenase (LDH) release assay involving co-treatment with tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and/or synthetic curcumin derivatives using TRAIL-resistant human CRT-MG astroglioma cells, the novel curcumin mimic library was found to effectively stimulate the cytotoxicity of TRAIL, causing mild cytotoxicity when administered alone. In particular, 11a and 11j are promising candidates for TRAIL-sensitizers with potential use in combination chemotherapy for brain tumors.

In vitro and in vivo activities of echinomycin against clinical isolates of Staphylococcus aureus.

OBJECTIVES: To verify in vitro and in vivo activities of echinomycin against clinical isolates of Staphylococcus aureus, we compared antistaphylococcal activities of echinomycin with those of vancomycin. METHODS: In vitro activities (MICs and MBCs) of oxacillin, vancomycin and echinomycin against 18 isolates of methicillin-susceptible S. aureus (MSSA) and 118 isolates of methicillin-resistant S. aureus (MRSA) were compared. Using four representative isolates of S. aureus, time-kill assay and in vivo antistaphylococcal activities were assessed. Echinomycin and vancomycin were compared in an in vivo mouse infection model. RESULTS: Echinomycin demonstrated higher in vitro activities against MSSA and MRSA strains, exhibiting 2-fold lower MIC(90)s and 4-fold lower MBC(90)s than vancomycin. Additionally, time-kill assay indicated that echinomycin is more potent than vancomycin against MSSA and MRSA strains in the context of MICs and MBCs. Using an in vivo protection model, it was shown that the 50% effective doses of echinomycin were at least 7-fold lower than those of vancomycin. Therefore, echinomycin displayed excellent protection in mice against acute peritoneal infections caused by both MSSA and MRSA strains. CONCLUSIONS: Collectively, these data indicate that the activity of echinomycin against S. aureus strains is at least equivalent to that of vancomycin, regardless of the methicillin resistance of these strains. These promising activities of echinomycin might justify its potential use against infections with S. aureus strains resistant to vancomycin. This might be the first report to show that echinomycin possesses antipathogenic staphylococcal activity.

Antidiabetic effects of chitosan oligosaccharides in neonatal streptozotocin-induced noninsulin-dependent diabetes mellitus in rats.

The antidiabetic effect of chitosan oligosaccharide (COS) was investigated in neonatal streptozotocin (STZ)-induced noninsulin-dependent diabetes mellitus rats. The fasting glucose level was reduced by about 19% in diabetic rats after treatment with 0.3% COS. Glucose tolerance was lower in the diabetic group compared with the normal group. After diabetic rats had been treated with 0.3% COS for 4 weeks, glucose tolerance increased significantly versus the diabetic control group, and glucose-inducible insulin expression increased significantly. In addition, fed-triglyceride (TG) levels in diabetic rats drinking 0.3% COS were reduced by 49% compared with those in diabetic control rats. The cholesterol levels of animals treated with COS were reduced by about 10% in fed or fasting conditions versus the corresponding controls, although the difference was not statistically significant. It was found that COS has a TG-lowering effect in diabetic rats, and that COS reduces signs of diabetic cardiomyopathy such as vacuolation of mitochondria and the separation and degeneration of myofibrils. In conclusion, these results indicate that COS can be used as an antidiabetic agent because it increases glucose tolerance and insulin secretion and decreases TG.

Chitosan oligosaccharides, dp 2-8, have prebiotic effect on the Bifidobacterium bifidium and Lactobacillus sp.

In order to investigate the prebiotic potential of chitosan oligosaccharide (COS), prepared by enzymatic hydrolysis of fully deacetylated chitosan polymer, the effect of COS on bacterial growth was studied. The degree of polymerization (dp) of COS was determined by MALDI-ToF mass spectrometry, and the COS was found to be composed of dimer (33.6%), trimer (16.9%), tetramer (15.8%), pentamer (12.4%), hexamer (8.3%), heptamer (7.1%), and octamer (5.9%). The minimum inhibitory concentrations (MIC) of chitosan polymer against lactic acid bacteria and bifidobacteria were below 0.31%. However, this only applied to two strains, the other bacteria tested grew on MRS broth containing 5% COS. The effects of COS on the growth of bifidobacteria and lactic acid bacteria were compared with those of fructo-oligosaccharide (FOS). FOS was found to have a growth stimulatory effect on only three strains: Bifidobacterium bifidium, B. infantis and Lactobacillus casei. However, COS stimulated the growth of most Lactobacillus sp. and B. bifidium KCTC 3440. The amount of the growth and the specific growth rate of B. bifidium increased with increasing COS concentration. The cultivation time required to obtain maximum growth was reduced to about 25% in MRS broth supplemented with 0.2-0.4% COS. These results demonstrate that COS has considerable bifidogenic potential. Both cell growth and specific growth rates of L. brevis in MRS broth supplemented with 0.1% COS increased by 25%. The present study shows that COS stimulates the growth of some enteric bacteria, and that COS has potential use as a prebiotic health-food.