Remote ischemic preconditioning in hemodialysis: a pilot study

Hemodialysis (HD)-induced myocardial ischemia is associated with an elevated cardiac troponin T, and is common in asymptomatic patients undergoing conventional HD. Remote ischemic preconditioning (RIPC) has a protective effect against myocardial ischemia–reperfusion injury. We hypothesized that RIPC also has a protective effect on HD-induced myocardial injury. Chronic HD patients were randomized to the control group or the RIPC group. RIPC was induced by transient occlusion of blood flow to the arm with a blood-pressure cuff for 5 min, followed by 5 min of deflation. Three cycles of inflation and deflation were undertaken before every HD session for 1 month (total 12 times). The primary outcome was the change in cardiac troponin T (cTnT) level at day 28 from baseline. Demographic and baseline laboratory values were not different between the control (n = 17) and the RIPC groups (n = 17). cTnT levels tended to decrease from day 2 in the RIPC group through to 28 days, in contrast to no change in the control group. There were significant differences in the change of cTnT level at day 28 from baseline [Control, median; ?0.002 ng/ml (interquartile range ?0.008 to 0.018) versus RIPC, median; ?0.015 ng/ml (interquartile range ?0.055 to 0.004), P = 0.012]. RIPC reduced cTnT release in chronic conventional HD patients, suggesting that this simple, cheap, safe, and well-tolerated procedure has a protective effect against HD-induced ischemia.     

Chromosome 13 deletion and hypodiploidy on conventional cytogenetics are robust prognostic factors in Korean multiple myeloma patients: web-based multicenter registry study

This study was designed to evaluate the prevalence of chromosomal abnormalities and to identify the specific abnormalities associated with poor prognosis. A total of 2,474 patients whose conventional cytogenetics were available at the time of diagnosis were evaluated via a nationwide registry. Normal metaphase cytogenetics was observed in 2,012 patients (81.3%). Among the 462 patients with chromosomal abnormalities, there were 161 (34.8%) patients with hyperdiploidy, 197 (42.6%) with pseudodiploidy, 79 (17.1%) with hypodiploidy, and 25 (5.5%) with near-tetraploidy. Deletion 13 (Δ13) in metaphase was observed in 167 patients (6.8%). Fluorescent in situ hybridization (FISH) was carried out in 967 patients (39.1%), and 66 (13.7%) out of 482 and 63 (10.3%) out of 611 patients were positive for t(4;14) and del(17p), respectively. With a median follow-up duration of 25.1 months, the median overall survival (OS) was 51.2 months (95% confidence interval, 46.5–55.9 months). In univariate analysis, the following four chromosomal abnormalities were significantly associated with a poor survival outcome: Δ13, hypodiploidy, del(13q) in FISH, and del(17p) in FISH. In the subsequent multivariate analysis, in which del(13q) and del(17p) in FISH were excluded due to a relatively low number of patients, Δ13 and hypodiploid status were independently associated with a poor survival outcome after adjusting for important clinical factors, including age, sex, performance, beta2-microglobulin, albumin, and lactate dehydrogenase (LDH). Using conventional metaphase cytogenetics, we confirmed that both Δ13 and hypodiploid status were robust poor prognostic factors. The metaphase karyotyping should remain the primary cytogenetic tool and an essential investigation for risk stratification in newly diagnosed multiple myeloma patients.     

A randomized,placebo-controlled,double-blind clinical trial of rikkunshito for patients with non-erosive reflux disease refractory to proton-pump inhibitor: the G-PRIDE study

Background

The aim of this study was to investigate the efficacy of rikkunshito (RKT), a traditional Japanese medicine, combined with proton pump inhibitor (PPI) in patients with PPI-refractory non-erosive reflux disease (NERD).

Methods

Patients with PPI-refractory NERD (n = 242) were randomly assigned to the RKT group [rabeprazole (10 mg/day) + RKT (7.5 g/t.i.d.) for 8 weeks] or the placebo group (rabeprazole + placebo). After the 4- and 8-week treatments, we assessed symptoms and quality of life (QOL) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG), Gastrointestinal Symptom Rating Scale (GSRS), and Short-Form Health Survey-8 (SF-8).

Results

There were no significant differences in FSSG and GSRS score improvement between these groups after the 4- and 8-week treatments. The mental component summary (MCS) scores of the SF-8 improved more in the RKT group (from 45.8 ± 8.1 to 48.5 ± 7.4) than in the placebo group (from 47.7 ± 7.1 to 48.4 ± 7.5) after the 4-week treatment (P < 0.05). The 8-week treatment with RKT was more effective for improvement of the degree of MCS score in patients with a low body mass index (<22) (P < 0.05) and significantly improved the acid-related dysmotility symptoms of FSSG in female and elderly patients (≥65 years).

Conclusion

There were no significant differences in improvement of GERD symptoms in patients with PPI-refractory NERD between these groups. However, RKT may be useful for improving mental QOL in non-obese patients and acid-related dyspeptic symptoms, especially in women and the elderly.     

APOE polymorphism and carotid atherosclerosis in Korean population: The Dong-gu Study and the Namwon Study

Objective

We evaluated the association between APOE polymorphism and carotid atherosclerosis in two large independent cohorts from South Korea.

Methods

The datasets were from the Dong-gu Study (N = 9056) and the Namwon Study (N = 10,158). Carotid ultrasonography was performed to measure carotid intima-media thickness (IMT) and the presence of carotid plaques. The APOE polymorphism was determined by PCR-RFLP. We performed combined and separate analyses for the two datasets.

Results

In the combined analysis, individuals with E2E2 or E2E3 genotype had a lower common carotid IMT compared with individuals with E3E3 genotype (0.684 mm vs. 0.736 mm, p = 0.007; 0.718 mm vs. 0.736 mm, p < 0.001, respectively). This association was very slightly attenuated but remained statistically significant after adjustment for blood lipids (0.690 mm vs. 0.736 mm, p = 0.033; 0.725 mm vs. 0.736 mm, p = 0.005, respectively). Compared with individuals with E3E3 genotype, individuals with E2E3 genotype had lower risk for carotid plaque (odds ratio (OR) = 0.83, 95% confidence interval (CI) = 0.75–0.93), while individuals with E3E4 genotype had a higher risk for carotid plaque (OR = 1.09, 95% CI = 1.00–1.20). After adjustment for blood lipids, ORs of E2E3 genotype for carotid plaque was slightly attenuated but remained significant (OR = 0.87 95% CI = 0.78–0.97), while OR of E3E4 genotype were slightly attenuated and not significant (OR = 1.08, 95% CI, 0.99–1.18).

Conclusions

We found that APOE polymorphism is associated with carotid atherosclerosis and this association was partly mediated through blood lipid. Our results suggest that APOE polymorphism may influence atherosclerosis through non-lipid pathways.     

Genomic Profiling of Patient-Derived Colon Cancer Xenograft Models

Recent evidence suggests that patient derived xenograft (PDX) models can maintain certain pathological and molecular features of the original disease. However, these characterizations are limited to immunohistochemistry or by tissue microarray analysis. We conducted a high-throughput sequencing of primary colon tumor and PDX has not been reported yet.Fresh primary colon cancer tissues that originate from surgery were implanted into the subcutaneous space of 6- to 8-week-old female BALB/c nu/nu or NOD/SCID mice and serially passaged in vivo. Ion AmpliSeq Cancer Hotspot Panel v2 (Ion Torrent) was used to detect frequent somatic mutations and similarity of molecular characteristics between the 10 patient tumors and matched PDX.Histologic and immunohistochemical analyses revealed a high degree of pathologic similarity including histologic architecture and expression of CEA, CK7, and CD20 between the patient and xenograft tumors. In 80% cases, all of the somatic mutations detected in primary tumor were concordantly detected in PDX models. However, 2 PDX models showed gained mutations such as PIK3CA or FBWX7 mutation.Ten patient-derived advanced colon cancer xenograft models were established. These models maintained the key characteristic features of the original tumors, suggesting useful tool for preclinical personalized medicine platform.     

Quantitative Prediction of Oral Bioavailability of a Lipophilic Antineoplastic Drug Bexarotene Administered in Lipidic Formulation Using a Combined In Vitro Lipolysis/Microsomal Metabolism Approach

For performance assessment of the lipid-based drug delivery systems (LBDDSs), in vitro lipolysis is commonly applied because traditional dissolution tests do not reflect the complicated in vivo micellar formation and solubilization processes. Much of previous research on in vitro lipolysis has mostly focused on rank-ordering formulations for their predicted performances. In this study, we have incorporated in vitro lipolysis with microsomal stability to quantitatively predict the oral bioavailability of a lipophilic antineoplastic drug bexarotene (BEX) administered in LBDDS. Two types of LBDDS were applied: lipid solution and lipid suspension. The predicted oral bioavailability values of BEX from linking in vitro lipolysis with microsomal stability for lipid solution and lipid suspension were 34.2 ± 1.6% and 36.2 ± 2.6%, respectively, whereas the in vivo oral bioavailability of BEX was tested as 31.5 ± 13.4% and 31.4 ± 5.2%, respectively. The predicted oral bioavailability corresponded well with the oral bioavailability for both formulations, demonstrating that the combination of in vitro lipolysis and microsomal stability can quantitatively predict oral bioavailability of BEX. In vivo intestinal lymphatic uptake was also assessed for the formulations and resulted in <1% of the dose, which confirmed that liver microsomal stability was necessary for correct prediction of the bioavailability.     

Promotion of Pt/CeO2 catalyst by hydrogen treatment for low-temperature CO oxidation

Low temperature CO oxidation reaction is known to be facilitated over platinum supported on a reducible cerium oxide. Pt species act as binding sites for reactant CO molecules, and oxygen vacancies on surface of cerium oxide atomically activate the reactant O₂ molecules. However, the impacts of size of Pt species and concentration of oxygen vacancy at the surface of cerium oxide on the CO oxidation reaction have not been clearly distinguished, thereby various diverse approaches have been suggested to date. Here using the co-precipitation method we have prepared pure ceria support and infiltrated it with Pt solution to obtain 0.5 atomic% Pt supported on cerium oxide catalyst, and then systematically varied the size of Pt from single atom to ∼1.7 nm sized nanoparticles and oxygen vacancy concentration at surface of cerium oxide by controlling the heat-treatment conditions, which are temperature and oxygen partial pressure. It is found that Pt nanoparticles in range of 1–1.7 nm achieve 100% of CO oxidation reaction at ∼100 °C lower temperature compared to Pt single atom owing to the facile adsorption of CO but weaker binding strength between Pt and CO molecules, and the oxygen vacancy in the vicinity of Pt accelerates CO oxidation below 150 °C. Based on this understanding, we show that a simple hydrogen reduction at 550 °C for the single atom Pt supported on CeO₂ catalyst induces the formation of highly dispersed Pt nanoparticles with size of 1.7 ± 0.2 nm and the higher concentration of surface oxygen vacancies simultaneously, enabling 100% conversion from CO to CO₂ at 200 °C as well as 16% conversion even at 150 °C owing to the synergistic effects of Pt nanoparticles and oxygen vacancies.

Understanding on effects of Pt size and oxygen vacancy at CeO₂ surface in Pt/CeO₂ catalyst for CO oxidation reaction enables to boost catalytic activity.