Clinical Outcomes of Ticagrelor in Korean Patients with Acute Myocardial Infarction without High Bleeding Risk

BackgroundAlthough ticagrelor is known to increase the bleeding risk compared to clopidogrel in East Asian patients, its clinical benefits in patients with acute myocardial infarction (AMI) without high bleeding risk (HBR) remains unknown.MethodsA total of 7,348 patients who underwent successful percutaneous coronary intervention (PCI) from the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), between November 2011 and December 2015, were divided into two groups according to the Academic Research Consortium for HBR criteria (KAMIR-HBR, 2,469 patients; KAMIR-non HBR, 4,879 patients). We compared in-hospital major adverse cardiovascular events (MACEs, defined as a composite of cardiac death, non-fatal myocardial infarction, or stroke), and the thrombolysis in myocardial infarction (TIMI) major bleeding between ticagrelor and clopidogrel in the KAMIR-HBR and the KAMIR-non HBR groups, respectively.ResultsAfter propensity score matching, ticagrelor had a higher incidence of in-hospital TIMI major bleeding than clopidogrel in all patients (odds ratio [OR], 1.683; 95% confidence interval [CI], 1.010–2.805; P = 0.046) and the KAMIR-HBR group (OR, 3.460; 95% CI, 1.374–8.714; P = 0.008). However, there was no significant difference in in-hospital TIMI major bleeding between ticagrelor and clopidogrel in the KAMIR-non HBR group (OR, 1.436; 95% CI, 0.722–2.855; P = 0.303). No differences were observed in the cumulative incidences of in-hospital and 6-month MACEs between ticagrelor and clopidogrel in both groups.ConclusionsThe bleeding risk of ticagrelor was attenuated in Korean patients with AMI without HBR. Appropriate patient selection could reduce in-hospital bleeding complications associated with ticagrelor in Korean patients with AMI who underwent successful PCI.     

Prevalence of Bladder Pain Syndrome-like Symptoms: a Population-based Study in Korea

ObjectivesTo investigate the prevalence of bladder pain syndrome (BPS)-like symptoms in the general population of South Korea.MethodsBetween April 16, 2016 and April 29, 2016, we conducted an online survey and computer-assisted personal interviews with adults aged 40–79 years in Korea using structured questionnaires. The sample size was 3,000 (95% confidence level standard error ± 1.79%), and the sampling method was simple randomization according to sex, age, and residential area in proportion to the resident registration demographics of the Korean Ministry of Interior and Safety as of March 2016. All participants were surveyed using the Korean version of the Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale and Geriatric Depression Scale (GDS). The primary outcome was the prevalence of BPS-like symptoms, defined as a total PUF score of ≥ 12.ResultsOverall, the prevalence of BPS-like symptoms was 16.4% (483 of 3,000 participants). Women (21.4%) had a significantly higher prevalence of BPS-like symptoms than men (10.7%) (P < 0.01). The prevalence by age was significantly higher in the 70s group than in the other age groups (P < 0.01), and increased significantly with the increasing severity of depression on the GDS (P < 0.01). The prevalence of BPS-like symptoms according to the marital status was significantly different, that is, the prevalence among divorced/bereaved individuals was higher than those of married or unmarried individuals (P < 0.01).ConclusionOur large, representative population-based study showed that BPS-like symptoms are widespread among the general population of South Korea. BPS is considered a disease that deserves greater attention as it is far more common than previously thought and can negatively affect many people''s quality of life.     

Alterations in extracellular matrix components in transplant glomerulopathy

The distribution pattern of extracellular matrix (ECM) components in transplant glomerulopathy was studied in relation to light microscopic features, actin expression of mesangial cells, and intraglomerular inflammatory cells. Nine cases of mild (group I) and nine cases of severe (group II) transplant glomerulopathy were stained with antisera against fibronectin (FN), tenascin (TN), collagen types III and IV, smooth muscle actin, CD45RO, CD68, and Ki-67 antigen. The composition of ECM was similar in the two groups. The expanded mesangium was diffusely stained by type-IV collagen, FN and TN, and focally and weakly stained by type-III collagen and smooth muscle actin. Type-IV collagen was linearly stained along the capillary walls, imparting a double-contour feature, whereas FN and TN showed granular staining along the capillary walls. CD68 positive cells were increased in severe transplant glomerulopathy, but this increase was not related to ECM deposition. These findings suggest that increased glomerular deposition of normal and abnormal ECM components participate in the evolution of transplant glomerulopathy. Received: 5 October 1999 / Accepted: 17 January 2000     

Decreased entropy of symbolic heart rate dynamics during daily activity as a predictor of positive head-up tilt test in patients with alleged neurocardiogenic syncope

Entropy measures of RR interval variability during daily activity over a 24h period were compared in 30 patients with a positive head-up tilt (HUT) test and 30 patients with a negative HUT test who had a history of alleged neurocardiogenic syncope. Two different entropies, approximate entropy (ApEn) and entropy of symbolic dynamics (SymEn), were employed. In patients showing a positive HUT test, the entropies were significantly decreased when compared with the patients with a negative HUT test. In addition, SymEn in the patients with a negative HUT test was significantly lower than in the normal controls. Discriminant analysis using SymEn could correctly identify 89.3% (520/582) of the 1 h RR interval data of the patients with a positive HUT test regardless of the time of day. Baseline entropies of heart rate dynamics during daily activity were found to be significantly lower in patients with alleged neurocardiogenic syncope and a positive HUT test than in those with the same history but with a negative HUT test. The decreased entropy of symbolic heart rate dynamics may be of predictive value of a positive HUT test in patients with alleged neurocardiogenic syncope.     

Caffeine, extended stress, and blood pressure in borderline hypertensive men

Caffeine increases blood pressure (BP), and its pressor effects are larger in borderline hypertensive (BH) men than in controls. This article extends findings of larger caffeine effects on BP at rest and to brief mental stress in BH to a new analysis of caffeine and prolonged mental stress in BH. In a double-blind, crossover study, 24 male BH (140/90 mmHg < BP < 160/95 mmHg) and 23 normotensive controls who were habitual caffeine consumers (NT; BP < 135/85 mmHg; negative parental history) worked on alternating mental stressors for 35 min after placebo or caffeine (3.3 mg/kg). Caffeine raised systolic blood pressure (SBP) and diastolic blood pressure (DBP) alone and during the extended tasks (all ps < .00001/.00001). BH had larger SBP and DBP increases over all postcaffeine periods (ps < .04/04) and larger DBP rises to the extended tasks after caffeine (p = .007). These combined effects led to undesirably high BPs (> 140/82 mmHg) relative to controls (< 130/75) during the 100 min after caffeine intake. Caffeine taken by BH at times of extended behavioral stress may elevate BP to a clinically meaningful degree. This research was supported by the Medical Research Service of the Department of Veterans Affairs and the National Heart Lung and Blood Institute of the National Institutes of Health, grant numbers HL32050 and HL07640. We thank Barbara McKey and Judith Silverstein for their efforts in data collection and Terrie Thomas for her valuable comments on an earlier version of this article.     

Genome-wide association study identifies breast cancer risk variant at 10q21.2: results from the Asia Breast Cancer Consortium

Although approximately 20 common genetic susceptibility loci have been identified for breast cancer risk through genome-wide association studies (GWASs), genetic risk variants reported to date explain only a small fraction of heritability for this common cancer. We conducted a four-stage GWAS including 17 153 cases and 16 943 controls among East-Asian women to search for new genetic risk factors for breast cancer. After analyzing 684 457 SNPs in 2062 cases and 2066 controls (Stage I), we selected for replication among 5969 Chinese women (4146 cases and 1823 controls) the top 49 SNPs that had neither been reported previously nor were in strong linkage disequilibrium with reported SNPs (Stage II). Three SNPs were further evaluated in up to 13 152 Chinese and Japanese women (6436 cases and 6716 controls) (Stage III). Finally, two SNPs were evaluated in 10 847 Korean women (4509 cases and 6338 controls) (Stage IV). SNP rs10822013 on chromosome 10q21.2, located in the zinc finger protein 365 (ZNF365) gene, showed a consistent association with breast cancer risk in all four stages with a combined per-risk allele odds ratio of 1.10 (95% CI: 1.07-1.14) (P-value for trend = 5.87 × 10(-9)). In vitro electrophoretic mobility shift assays demonstrated the potential functional significance of rs10822013. Our results strongly implicate rs10822013 at 10q21.2 as a genetic risk variant for breast cancer among East-Asian women.     

Effects of chitosan-nanoparticle-mediated tight junction opening on the oral absorption of endotoxins

Recently, we reported a pH-responsive nanoparticle (NP) system shelled with chitosan (CS), which could effectively increase the oral absorption of insulin and produce a hypoglycemic effect, presumably due to the CS-mediated tight junction (TJ) opening. It has been often questioned whether CS can also enhance the absorption of endotoxins present in the small intestine. To address this concern, we studied the effect of CS NPs on the absorption of lipopolysaccharide (LPS), the most commonly found toxin in the gastrointestinal tract. To follow their biodistribution by the single-photon emission computed tomography/computed tomography, LPS and insulin were labeled with (99m)Tc-pertechnetate ((99m)Tc-LPS) and (123)iodine ((123)I-insulin), respectively. The (99m)Tc-LPS was ingested 1 h prior to the administration of the (123)I-insulin-loaded NPs to mimic the physiological conditions. The confocal and TEM micrographs show that the orally administered CS NPs were able to adhere and infiltrate through the mucus layer, approach the epithelial cells and mediate to open their TJs. The radioactivity associated with LPS was mainly restricted to the gastrointestinal tract, whereas (123)I-insulin started to appear in the urinary bladder at 3 h post administration. This observation indicates that the insulin-loaded in CS NPs can traverse across the intestinal epithelium and enter the systemic circulation, whereas LPS was unable to do so, probably because of the charge repulsion between the anionic LPS in the form of micelles and the negatively charged mucus layer. Our in vivo toxicity study further confirms that the enhancement of paracellular permeation by CS NPs did not promote the absorption of LPS. These results suggest that CS NPs can be used as a safe carrier for oral delivery of protein drugs.     

Mechanisms of the contextual interference effect in individuals poststroke

Although intermixing different motor learning tasks via random schedules enhances long-term retention compared with "blocked" schedules, the mechanism underlying this contextual interference effect has been unclear. Furthermore, previous studies have reported inconclusive results in individuals poststroke. We instructed participants to learn to produce three grip force patterns in either random or blocked schedules and measured the contextual interference effect by long-term forgetting: the change in performance between immediate and 24-h posttests. Nondisabled participants exhibited the contextual interference effect: no forgetting in the random condition but forgetting in the blocked condition. Participants at least 3 mo poststroke exhibited no forgetting in the random condition but marginal forgetting in the blocked condition. However, in participants poststroke, the integrity of visuospatial working memory modulated long-term retention after blocked schedule training: participants with poor visuospatial working memory exhibited little forgetting at 24 h. These counterintuitive results were predicted by a computational model of motor memory that contains a common fast process and multiple slow processes, which are competitively updated by motor errors. In blocked schedules, the fast process quickly improved performance, therefore reducing error-driven update of the slow processes and thus poor long-term retention. In random schedules, interferences in the fast process led to slower change in performance, therefore increasing error-driven update of slow processes and thus good long-term retention. Increased forgetting rates in the fast process, as would be expected in individuals with visuospatial working memory deficits, led to small updates of the fast process during blocked schedules and thus better long-term retention.     

Placenta percreta-induced uterine rupture diagnosed by laparoscopy in the first trimester

Spontaneous uterine rupture is lethal in pregnant women. Placenta percreta-induced spontaneous uterine rupture in the first trimester is extremely rare and difficult to diagnose. A 35-year-old pregnant woman, with a history of 2 vaginal deliveries and 2 spontaneous abortions treated by dilatation and curettage, was admitted to the emergency department because of sudden severe abdominal pain; the gestational age as calculated by sonography was 14 weeks. Diagnostic laparoscopy was considered for surgical abdomen and fluid collection that was noted in sonography. During laparoscopy, uterine rupture with massive bleeding was detected; therefore, total abdominal hysterectomy was performed. The patient was discharged without any complications. Pathological analysis of the uterine specimen revealed placenta percreta to be the cause of the rupture. Uterine rupture should be considered in the differential diagnosis in all pregnant women who present with acute abdomen, show fluid collection in the peritoneal cavity. In addition, we recommend laparoscopy for the investigation of acute abdomen with unclear diagnosis in the first trimester of pregnancy.