Distal Radial Access for Coronary Procedures in a Large Prospective Multicenter Registry: The KODRA Trial.

BACKGROUND: Distal radial access (DRA) as an alternative access route lacks evidence, despite its recent reputation. OBJECTIVES: The aim of this study was to evaluate the safety and feasibility of DRA on the basis of daily practice. METHODS: The KODRA (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach) trial was a prospective multicenter registry conducted at 14 hospitals between September 2019 and September 2021. The primary endpoints were the success rates of coronary angiography (CAG) and percutaneous coronary intervention (PCI). The secondary endpoints included successful distal radial artery puncture, access-site crossover, access site-related complications, bleeding events, and predictors of puncture failure. RESULTS: A total of 4,977 among 5,712 screened patients were recruited after the exclusion of 735 patients. The primary endpoints, the success rates of CAG and PCI via DRA, were 100% and 98.8%, respectively, among successful punctures of the distal radial artery (94.4%). Access-site crossover occurred in 333 patients (6.7%). The rates of distal radial artery occlusion and radial artery occlusion by palpation were 0.8% (36 of 4,340) and 0.8% (33 of 4,340) at 1-month follow-up. DRA-related bleeding events were observed in 3.3% of patients, without serious hematoma. Multilevel logistic regression analysis identified weak pulse (OR: 9.994; 95% CI: 7.252-13.774) and DRA experience <100 cases (OR: 2.187; 95% CI: 1.383-3.456) as predictors of puncture failure. CONCLUSIONS: In this large-scale prospective multicenter registry, DRA demonstrated high success rates of CAG and PCI, with a high rate of puncture success but low rates of distal radial artery occlusion, radial artery occlusion, bleeding events, and procedure-related complications. Weak pulse and DRA experience <100 cases were predictors of puncture failure. (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach [KODRA]; NCT04080700).

Impact of Hospital Volume of Percutaneous Coronary Intervention (PCI) on In-Hospital Outcomes in Patients with Acute Myocardial Infarction: Based on the 2014 Cohort of the Korean Percutaneous Coronary Intervention (K-PCI) Registry.

BACKGROUND AND OBJECTIVES: The relationship between the hospital percutaneous coronary intervention (PCI) volumes and the in-hospital clinical outcomes of patients with acute myocardial infarction (AMI) remains the subject of debate. This study aimed to determine whether the in-hospital clinical outcomes of patients with AMI in Korea are significantly associated with hospital PCI volumes. METHODS: We selected and analyzed 17,121 cases of AMI, that is, 8,839 cases of non-ST-segment elevation myocardial infarction and 8,282 cases of ST-segment elevation myocardial infarction, enrolled in the 2014 Korean percutaneous coronary intervention (K-PCI) registry. Patients were divided into 2 groups according to hospital annual PCI volume, that is, to a high-volume group (≥400/year) or a low-volume group (<400/year). Major adverse cardiovascular and cerebrovascular events (MACCEs) were defined as composites of death, cardiac death, non-fatal myocardial infarction (MI), stent thrombosis, stroke, and need for urgent PCI during index admission after PCI. RESULTS: Rates of MACCE and non-fatal MI were higher in the low-volume group than in the high-volume group (MACCE: 10.9% vs. 8.6%, p=0.001; non-fatal MI: 4.8% vs. 2.6%, p=0.001, respectively). Multivariate regression analysis showed PCI volume did not independently predict MACCE. CONCLUSIONS: Hospital PCI volume was not found to be an independent predictor of in-hospital clinical outcomes in patients with AMI included in the 2014 K-PCI registry.

A deep learning algorithm may automate intracranial aneurysm detection on MR angiography with high diagnostic performance.

OBJECTIVES: To develop a deep learning algorithm for automated detection and localization of intracranial aneurysms on time-of-flight MR angiography and evaluate its diagnostic performance. METHODS: In a retrospective and multicenter study, MR images with aneurysms based on radiological reports were extracted. The examinations were randomly divided into two data sets: training set of 468 examinations and internal test set of 120 examinations. Additionally, 50 examinations without aneurysms were randomly selected and added to the internal test set. External test data set consisted of 56 examinations with intracranial aneurysms and 50 examinations without aneurysms, which were extracted based on radiological reports from a different institution. After manual ground truth segmentation of aneurysms, a deep learning algorithm based on 3D ResNet architecture was established with the training set. Its sensitivity, positive predictive value, and specificity were evaluated in the internal and external test sets. RESULTS: MR images included 551 aneurysms (mean diameter, 4.17 ± 2.49 mm) in the training, 147 aneurysms (mean diameter, 3.98 ± 2.11 mm) in the internal test, 63 aneurysms (mean diameter, 3.23 ± 1.69 mm) in the external test sets. The sensitivity, the positive predictive value, and the specificity were 87.1%, 92.8%, and 92.0% for the internal test set and 85.7%, 91.5%, and 98.0% for the external test set, respectively. CONCLUSION: A deep learning algorithm detected intracranial aneurysms with a high diagnostic performance which was validated using external data set. KEY POINTS: • A deep learning-based algorithm for the automated diagnosis of intracranial aneurysms demonstrated a high sensitivity, positive predictive value, and specificity. • The high diagnostic performance of the algorithm was validated using external test data set from a different institution with a different scanner. • The algorithm might be robust and effective for general use in real clinical settings.

"The Renal Foot" - Angiographic Pattern of Patients with Chronic Limb Threatening Ischemia and End-Stage Renal Disease.

BACKGROUND: Patients with chronic limb threatening ischemia (CLTI) and end-stage renal disease (ESRD) have greater risk of limb loss compared to those with CLTI alone. We investigated angiographic patterns in patients with CLTI and evaluated for differences based on ESRD status. METHODS: We reviewed lower extremity angiograms of 152 CLTI patients at a single academic medical center from 2011 to 2017 and analyzed them based on the Graziani and Bollinger classification systems. We used these classification systems to evaluate for angiographic patterns and arterial disease severity categorized by the presence or absence of ESRD. RESULTS: The analysis included 152 CLTI patients (161 angiograms). Patients' mean age was 63.4 ±â€¯11.3 years and 20 (12.4%) patients had ESRD. In our study population, infrapopliteal arterial disease was more severe than femoropopliteal disease. Disease of the arteries providing direct flow to the plantar arch was more severe in ESRD patients compared to non-ESRD patients, evident by higher Graziani Class VII disease (20% vs. 4.9%, p = .03). ESRD patients also had higher rates of concurrent significant stenosis of the posterior tibial and lateral plantar arteries (70% vs. 23%, p < .0001). CONCLUSION: In people with CLTI, infrapopliteal arteries are more severely affected than proximal femoropopliteal arteries. ESRD patients exhibit a pattern of arterial disease, we termed the "renal foot," that frequently involves arteries providing direct flow to the plantar arch.

Elevation of heart-femoral pulse wave velocity by short-term low sodium diet followed by high sodium diet in hypertensive patients with sodium sensitivity.

BACKGROUND/OBJECTIVES: We compared changes in heart-femoral pulse wave velocity (hfPWV) in response to low sodium and high sodium diet between individuals with sodium sensitivity (SS) and resistance (SR) to evaluate the influence of sodium intake on arterial stiffness. SUBJECTS/METHODS: Thirty-one hypertensive and 70 normotensive individuals were given 7 days of low sodium dietary approach to stop hypertension (DASH) diet (LSD, 100 mmol NaCl/day) followed by 7 days of high sodium DASH diet (HSD, 300 mmol NaCl/day) during 2 weeks of hospitalization. The hfPWV was measured and compared after the LSD and HSD. RESULTS: The hfPWV was significantly elevated from LSD to HSD in individuals with SS (P = 0.001) independently of changes in mean arterial pressure (P = 0.037). Conversely, there was no significant elevation of hfPWV from LSD to HSD in individuals with SR. The percent change in hfPWV from the LSD to the HSD in individuals with SS was higher than that in individuals with SR. Subgroup analysis revealed that individuals with both SS and hypertension showed significant elevation of hfPWV from LSD to HSD upon adjusted analysis using changes of the means arterial pressure (P = 0.040). However, there was no significant elevation of hfPWV in individuals with SS and normotension. CONCLUSION: High sodium intake elevated hfPWV in hypertensive individuals with SS, suggesting that high sodium intake increases aortic stiffness, and may contribute to enhanced cardiovascular risk in hypertensive individuals with SS.

Glucose-insulin-potassium solution protects ventricular myocytes of neonatal rat in an in vitro coverslip ischemia/reperfusion model.

BACKGROUND AND OBJECTIVES: The benefit of high glucose-insulin-potassium (GIK) solution in clinical applications is controversial. We established a neonatal rat ventricular myocyte (NRVM) in vitro coverslip ischemia/reperfusion (I/R) model and investigated the effects of GIK solution on suppressing reactive oxygen species (ROS) and upregulating O-GlcNacylation, which protects cells from ischemic injury. MATERIALS AND METHODS: NRVMs were isolated from postnatal day 3-4 Sprague-Dawley rat pups and grown in Dulbecco's modified Eagle's medium containing high glucose (4.5 g/L), fetal bovine serum, and penicillin/streptomycin. The effects of the GIK solution on ROS production, apoptosis, and expression of O-GlcNAc and O-GlcNAc transferase (OGT) were investigated in the coverslip I/R model. RESULTS: Covering the 24-well culture plates for 3 hr with 12 mm diameter coverslips resulted in the appropriate ischemic shock. Glucose and insulin synergistically reduced ROS production, protected NRVM dose-dependently from apoptosis, and altered O-GlcNAc and OGT expression. CONCLUSION: The high GIK solution protected NRVM from I/R injury in vitro by reducing ROS and altering O-GlcNacylation.

A case of popliteal artery entrapment syndrome presenting with acute limb ischaemia.

Popliteal artery entrapment syndrome (PAES) is caused by an anomalous anatomic relationship between the popliteal artery and the musculotendinous structures in the popliteal fossa. In the early stage of PAES, patients most commonly present with intermittent claudication. If we don't perform appropriate investigation, the diagnosis of PAES is easily missed and may lead to irreversible arterial damage. Thrombus formation in the damaged popliteal artery can cause complete obstruction of the popliteal artery leading to acute limb-threatening ischaemia.

High sodium intake in women with metabolic syndrome.

BACKGROUND AND OBJECTIVES: Metabolic syndrome and high sodium intake are associated with frequent cardiovascular events. Few studies have estimated sodium intake in subjects with metabolic syndrome by 24-hour urine sodium excretion. We evaluated sodium intake in individuals with metabolic syndrome. SUBJECTS AND METHODS: Participants were recruited by random selection and through advertisement. Twenty four-hour urine collection, ambulatory blood pressure measurements, and blood test were performed. Sodium intake was estimated by 24-hour urine sodium excretion. Participants receiving antihypertensive medications were excluded from analysis. RESULTS: Among the 463 participants recruited, subjects with metabolic syndrome had higher levels of 24-hour urine sodium excretion than subjects without metabolic syndrome (p=0.0001). There was a significant relationship between the number of metabolic syndrome factors and 24-hour urine sodium excretion (p=0.001). The proportion of subjects with metabolic syndrome was increased across the tertile groups of 24-hour urine sodium excretion (p<0.0001). The association of high sodium intake and metabolic syndrome was significant only among women. Among the factors related to metabolic syndrome, body mass index had an independent association with 24-hour urine sodium excretion (p<0.0001). CONCLUSION: Women with metabolic syndrome exhibited significantly higher sodium intake, suggesting that dietary education to reduce sodium consumption should be emphasized for women with metabolic syndrome.

Brachial-ankle pulse wave velocity for the prediction of the presence and severity of coronary artery disease.

The predictability of brachial-ankle pulse wave velocity (baPWV) for the presence and severity of coronary artery disease (CAD) was investigated by measuring baPWV in 501 subjects scheduled for coronary angiography. Severity of CAD was measured using modified Gensini stenosis score (GSS) and classified as a vessel disease score (VDS) of 0-3. The presence of CAD was defined as diameter stenosis>50%. Subjects were grouped in tertile by level of baPWV (<14, 14-17, >17 m/s). Subjects with CAD showed higher mean age, prevalence of men and diabetes, and systolic blood pressure. The prevalence of hypertension, use of antihypertensive medications and use of statin was not different. Subjects with CAD had higher baPWV than subjects without CAD (16.70 ± 3.46 versus 15.21 ± 3.19 m/s, p<0.001). Multiple linear regression analysis showed significant correlation of baPWV and modified GSS (p=0.0337). ANCOVA adjusted with age, gender, body mass index, presence of hypertension or diabetes, status of smoking, use of antihypertensive medications and risk of hypercholesterolemia showed a statistically significant association of baPWV with VDS (p<0.0001). Highest tertile of baPWV had a statistically significant effect on the severity of CAD from an ANCOVA model. The predictive power of highest tertile of baPWV for the presence of CAD was 3.600 [95% confidence interval (CI) 1.884-6.881, p<0.0001]. It is concluded that increased baPWV is a reliable predictor of the presence and severity of CAD, suggesting that baPWV>17 m/s may be a threshold value for the presence and severity of CAD.

Severe hyperkalemia can be detected immediately by quantitative electrocardiography and clinical history in patients with symptomatic or extreme bradycardia: a retrospective cross-sectional study.

PURPOSE: Detecting severe hyperkalemia is challenging. We explored its prevalence in symptomatic or extreme bradycardia and devised a diagnostic rule. MATERIALS AND METHODS: This retrospective cross-sectional study included patients with symptomatic (heart rate [HR] ≤ 50/min with dyspnea, chest pain, altered mentality, dizziness/syncope/presyncope, general weakness, oliguria, or shock) or extreme (HR ≤ 40/min) bradycardia at an emergency department for 46 months. Risk factors for severe hyperkalemia were chosen by multiple logistic regression analysis from history (sex, age, comorbidities, and medications), vital signs, and electrocardiography (ECG; maximum precordial T-wave amplitude, PR, and QRS intervals). The derived diagnostic index was validated using bootstrapping method. RESULTS: Among the 169 participants enrolled, 87 (51.5%) were female. The mean (SD) age was 71.2 (12.5) years. Thirty-six (21.3%) had severe hyperkalemia. The diagnostic summed "maximum precordial T ≥ 8.5 mV (2)," "atrial fibrillation/junctional bradycardia (1)," "HR ≤ 42/min (1)," "diltiazem medication (2)," and "diabetes mellitus (1)." The C-statistics were 0.86 (0.80-0.93) and were validated. For scores of 4 or higher, sensitivity was 0.50, specificity was 0.92, and positive likelihood ratio was 6.02. The "ECG-only index," which sums the 3 ECG findings, had a sensitivity of 0.50, specificity of 0.90, and likelihood ratio (+) of 5.10 for scores of 3 or higher. CONCLUSIONS: Severe hyperkalemia is prevalent in symptomatic or extreme bradycardia and detectable by quantitative electrocardiographic parameters and history.

Subclinical renal insufficiency range of estimated glomerular filtration rate and microalbuminuria are independently associated with increased arterial stiffness in never treated hypertensives.

BACKGROUND AND OBJECTIVES: Microalbuminuria (MAU) and decreased estimated glomerular filtration rate (eGFR) are risk factors for cardiovascular disease (CVD) in patients with hypertension. However, in hypertensive patients with normal or minimally reduced eGFR (≥60 mL/min/1.73 m(2)) and with normo- or MAU, the value of combined estimation of eGFR and urine microalbumin for the risk assessment has not been widely reported. We evaluated the association between arterial stiffness and the combined estimation of eGFR and urine microalbumin. SUBJECTS AND METHODS: Subjects with never treated hypertension and normal or minimally reduced eGFR were evaluated (n=491, 50.1±10.4 years). eGFR was calculated by the simplified Modification of Diet in Renal Disease formula. Urinary albumin-to-creatinine ratio (UACR) was assessed with spot urine. Arterial stiffness was assessed with heart-femoral pulse wave velocity (hfPWV). All subjects were divided into four groups; group 1, eGFR ≥90 mL/min/1.73 m(2) (normal eGFR) and normo-albuminuria (NAU); group 2, eGFR 89.9-60 mL/min/1.73 m(2) (minimally reduced eGFR) and NAU; group 3, normal eGFR and MAU; group 4, minimally reduced eGFR and MAU. RESULTS: Group 1 had the lowest hfPWV (964.6±145.4; group 2, 1013.5±168.9; group 3, 1058.2±238.0; group 4, 1065.8±162.9 cm/sec). Analysis adjusting age, sex, body mass index, heart rate and mean arterial pressure showed significantly lower hfPWV of group 1 compared to group 2 (p=0.032) and 3 (p=0.007). Multiple regression analysis showed a significant association of hfPWV with logUACR {beta=0.096, 95% confidence interval (CI) 8.974-60.610, p=0.008} and eGFR (beta=-0.069, 95% CI -1.194 - -0.005, p=0.048). CONCLUSION: Minimally reduced eGFR or MAU is independently associated with increased arterial stiffness, indicating greater CVD risk.

Percutaneous Transluminal Angioplasty of Contralateral Iliac and Superficial Femoral Arteries via Graft Vessel in a Patient with FemoroFemoral Bypass Graft.

Peripheral arterial disease represents a significant problem, particularly among the elderly population. There has been great progress made in the treatment of peripheral arterial disease in recent years. Percutaneous transluminal angioplasty (PTA) has been employed as a method of treatment for patients with a variety of peripheral arterial disease. We report our experience with PTA of contralateral common iliac and superficial femoral arteries via graft vessel in a patient with femorofemoral bypass due to ipsilateral iliac artery occlusion.

RGS2 is a negative regulator of STAT3-mediated Nox1 expression.

NADPH oxidase 1 (Nox1) is essential for reactive oxygen species production in the innate immune responses mediated by toll-like receptor (TLR), but the mechanism regulating its expression remains uncertain. Here, we find that Nox1 induction is TLR2-dependent, but independent of myeloid differentiation primary response gene 88 (MyD88). We demonstrate the capacity of signal transducer and activator of transcription 3 (STAT3) to activate Nox1's transcription, as well as cooperative regulation by janus kinase 1 and 3 (JAK1 and JAK3). We find that regulator of G-protein signaling 2 (RGS2) inhibits STAT3-mediated Nox1 transcription, and can itself be repressed by TLR2; Nox1 induction upon RGS2 down-regulation is controlled by protein kinase C-η (PKC-η) and phospholipase D2 (PLD2). A GFP-tagged version of RGS2 concentrates in the nucleus; RGS2 additionally directly binds STAT3 to regulate its transcriptional activity through TLR2 stimulation. Cumulatively, these results suggest that TLR2 signaling enhances Nox1 expression through the JAK1/3-STAT3 pathway, and that RGS2, through its regulation by the PKC-η/PLD2 pathway, represses STAT3's transcriptional activation of Nox1.

Increasing trend in the number of severe hypoglycemia patients in Korea.

BACKGROUND: To investigate whether the number of subjects with severe hypoglycemia who are brought to a hospital emergency department is increasing and to identify whether there have been changes in the demographic and clinical characteristics of those subjects. METHODS: We analyzed data from the Emergency Departments of two general hospitals in Seoul, Korea. We included data from all adult subjects with type 2 diabetes who presented to an emergency department with severe hypoglycemia between January 1, 2004 and December 30, 2009. RESULTS: A total of 740 cases of severe hypoglycemia were identified. The mean subject age was 69±12 years, mean duration of diabetes was 13.8±9.3 years, and 53.2% of subjects were receiving insulin therapy. We observed a sharp rise in the number of cases between 2006 and 2007. Stages 3-5 chronic kidney disease was diagnosed in 31.5% of subjects, and low C-peptide levels (<0.6 ng/mL) were found in 25.5%. The mean subject age, duration of diabetes, HbA1c level, and renal and insulin secretory function values did not change significantly during the study period. The proportion of glimepiride use increased, while use of gliclazide decreased among sulfonylurea users. Use of insulin analogues increased, while use of NPH/RI decreased among insulin users. CONCLUSION: We identified a sharp increase in the number of subjects with severe hypoglycemia presenting to an emergency room since 2006. The clinical characteristics of these subjects did not change markedly during the study period. Nationwide studies are warranted to further clarify this epidemic of severe hypoglycemia.

Frequency and related factors of masked hypertension at a worksite in Korea.

OBJECTIVES: Masked hypertension is associated with metabolic risks and increased risk of cardiovascular disease. The purpose of this study was to identify the frequency of and risk factors of masked hypertension in Korean workers. METHODS: The study was conducted among 121 employees at a hotel in Gyeongju, Korea, from December 2008 to February 2009. We measured blood pressure (BP) both in the clinic and using 24-hour ambulatory BP monitors for all subjects. Hypertension was defined independently by both methods, and subjects were classified into four groups: true normotension, masked hypertension, white coat hypertension, and sustained hypertension. RESULTS: The frequency of masked hypertension in our study group was 25.6%. Compared with true normotension, the factors related to masked hypertension were male gender (odds ratio [OR], 10.7; 95% confidence interval [CI], 1.41 to 81.09), aging one year (OR, 0.88; 95% CI, 0.78 to 0.99), clinic BP 120-129/80-84 mmHg (OR, 8.42; 95% CI, 1.51 to 46.82), clinic BP 130-139 / 85-89 mmHg (OR, 12.14; 95% CI, 1.80 to 81.85), smoking (OR, 5.51; 95% CI, 1.15 to 26.54), and increase of total cholesterol 1 mg / dL (OR, 1.05; 95% CI, 1.02 to 1.08). In males only, these factors were clinic BP 120-129 / 80-84 mmHg (OR, 15.07; 95% CI, 1.55 to 146.19), clinic BP 130-139 / 85-89 mmHg (OR, 17.16; 95% CI, 1.56 to 189.45), smoking (OR, 11.61; 95% CI, 1.52 to 88.62), and increase of total cholesterol 1 mg/dL (OR, 1.05; 95% CI, 1.01 to 1.09). CONCLUSIONS: The frequency of masked hypertension was high in our study sample. Detection and management of masked hypertension, a known strong predictor of cardiovascular risk, could improve prognosis for at-risk populations.

Effect of Korean red ginseng on arterial stiffness in subjects with hypertension.

OBJECTIVES: Korean red ginseng (KRG) improves endothelial function and lower blood pressure (BP), which may affect arterial stiffness. The present study evaluated whether KRG treatment could improve arterial stiffness in subjects with hypertension. SUBJECTS AND METHODS: Eighty (80) participants with hypertension who were treated with antihypertensive agents were randomly assigned to an active (KRG 3 g/day) or a placebo treatment group in a double-blind manner. Participants were not allowed to change their antihypertensive medications. Systolic BP (SBP) and diastolic BP (DBP) were measured at baseline, and at 1, 2, and 3 months. Arterial stiffness was assessed by the measurement of brachial-ankle pulse wave velocity (baPWV) at baseline, and at 1 and 3 months. RESULTS: Thirty (30) subjects in the active group (AG) and 34 subjects in the placebo group (PG) completed 3 months of treatment and then a per-protocol analysis was done. SBP and DBP at baseline, and at 1, 2, and 3 months were not different between the AG and PG (p>0.05). After 3 months of treatment, SBP of AG was not changed from SBP at baseline. However, DBP of AG, and SBP and DBP of PG after 3 months of treatment were significantly reduced (p<0.05). baPWV of both groups was significantly reduced at 1 and 3 months (p<0.05), but was not different between the groups at each time point. Analysis after adjustment for age, time-dependent mean arterial BP, heart rate, and levels of fasting blood glucose and triglycerides showed no significant difference between AG and PG in changes of baPWV from baseline to 1 and 3 months (p>0.05). CONCLUSIONS: Three (3) months' treatment with KRG did not improve arterial stiffness in subjects with hypertension.

Titanium dioxide inclusion in backing reduce the photoallergenicity of ketoprofen transdermal patch.

Ketoprofen (KP) is a widely used transdermal non-steroidal anti-inflammatory drug. However, increasing number of adverse effect case reports suggests that KP transdermal formulation can cause photoallergic reaction. The photoallergic potential of KP is attributable to the instability of KP under UV/visible light and subsequent formation of reactive degradation products. In this study, we investigated whether the inclusion of titanium dioxide (TiO(2)), a well-known mineral sunscreen agent, in the KP transdermal patch can prevent the photodegradation of KP and ultimately, can reduce photoallergic reaction. TiO(2) inclusion in fabric backing effectively decreased the UV transmission through fabric patch throughout all UVA region from 320 to 380 nm and consistently, KP patch with TiO(2) exhibited significantly increased photostability of KP. This enhanced photostability of KP resulted in reduced generation of photodegradation product as determined by HPLC-UV analysis. In a good accordance with these in vitro results, photosensitization test in guinea pig in vivo demonstrated low photoallergic reactions of KP patch with TiO(2) compared to KP patch without TiO(2), indeed. This study demonstrated that KP transdermal patch with TiO(2)-included backing can provide with improved photostability and photosafety over conventional fabric KP patch.

Long acting porous microparticle for pulmonary protein delivery.

This study investigated the porous-microparticle (PM) with low mass density and large size for pulmonary drug delivery. PM was prepared by the water-in-oil-in-water (W(1)/O/W(2)) multi-emulsion method with cyclodextrin derivative as a porogen and a stabilizer of peptide drugs. Herein, sucrose ethyl acetate (SAIB) was incorporated in PM for long acting protein release. In vitro release studies, the rapid release rate of proteins from PM was reduced due to the high viscosity of the added SAIB. As a result, BSA release from PM continued up to 7 days. This result suggests that PM having sustained release characteristics may be successfully applied for long-term pulmonary administration of protein or peptide drug. In addition, it is expected that these particles arrive at a deep lung epithelium due to low density (high porosity) and limit macrophage recognition because of big particle size (more than 5 microm).

Protein release behavior from porous microparticle with lysozyme/hyaluronate ionic complex.

Porous microparticles (PMs) with a low density (<0.4 g/cm3) for pulmonary protein delivery were prepared by the water-in-oil-in-water (W1/O/W2) multi-emulsion method using a cyclodextrin derivative as a porogen. The complexation of positively charged lysozyme (Lys) and negative-charged hyaluronate (HA) was investigated for long-term protein release from PMs. The interaction of Lys and HA not only increased protein encapsulation efficiency but also stabilized Lys against a denaturing organic solvent (dichloromethane). Furthermore, PMs with Lys/HA complexes increased the Lys release period up to 7 days, as opposed to a 4h Lys release time from PMs without Lys/HA complexes. In particular, PMs containing 10mg of HA and 50mg of Lys showed almost zero-order Lys release kinetic for 7 days and preserved the bioactivity of Lys more than 98% during its entire release period. This result suggests that PMs with Lys/HA complexes may be applied in long-term pulmonary administration of protein or peptide drugs, including those that require particles to arrive at a deep lung epithelium with the help of low density (high porosity) of PMs.

Prediction of paroxysmal atrial fibrillation using nonlinear analysis of the R-R interval dynamics before the spontaneous onset of atrial fibrillation.

BACKGROUND: New methods based on nonlinear theory have been developed to give more insight into complex heart rate (HR) dynamics. This study was designed to test the hypothesis that altered HR dynamics, as analyzed with complexity and fractal measures, may precede the spontaneous onset of paroxysmal atrial fibrillation (PAF). Secondly, the difference in the temporal change of these measurements between the different types of atrial fibrillation (AF) was assessed. METHODS AND RESULTS: From 105 Holter tapes in which PAF was recorded, 44 PAF (>or=5 min) episodes in 33 patients (22 men, 58 +/- 12 years), preceded by sinus rhythm for more than 1 h, were selected and submitted to time-and frequency-domain HR variability analyses, along with detrended fluctuation analysis, approximate entropy (ApEn) and sample entropy (SampEn). The 60 min before the onset of AF were divided into 6 10-min periods and studied using repeated measures ANOVA. PAF episodes were divided into 3 subgroups: an increased HF component and decreased L/H ratio (vagal type, n=20); increased L/H ratio and decreased HF component (sympathetic type, n=14); and non-related type (n=10). None of the time- or frequency-domain parameters showed any significant change before AF in any type of AF. The alpha(1) showed a tendency to decrease before the onset of AF and the change in alpha(1) was divergent according to the AF type. The ApEn decreased before the onset of AF (1.005+/-0.046, 60-50 min before AF to 0.894+/-0.052, 10-0 min before AF; p=0.032). The SampEn also decreased progressively before the start of AF (1.165 +/- 0.085, 60-50 min before AF to 0.887 +/- 0.077, 10-0 min before AF, p=0.003). The decrease in both the ApEn and SampEn was irrespective of the AF type. CONCLUSIONS: A reduction in the ApEn and SampEn, which reflects the nonlinear complexity of HR variability, is a hallmark of altered HR dynamics preceding the spontaneous onset of AF.