Aesthetic doctors' perception and attitudes toward tolerance in botulinum toxin.

BACKGROUND: Botulinum toxin is a crucial therapeutic tool with broad indications in both cosmetic and medical fields. However, the expanding cosmetic use and increased dosages of botulinum toxin have raised concerns about resistance, making it essential to study the awareness and management practices among healthcare professionals. METHODS: A survey was conducted among clinical physicians using botulinum toxin. The study investigated their experiences, awareness, and management practices related to toxin resistance. Real-time mobile app-based surveys were administered to clinicians attending the 45th International Academic Conference of the Korean Academy of Laser and Dermatology (KALDAT) on December 3, 2023. RESULTS: Among 3140 participants, 673 clinical physicians completed the survey. Of these, 363 clinicians (53.9%) reported experiencing botulinum toxin resistance. Regarding the resistance rate, 59.4% indicated less than 1%, 36% reported approximately 1%-25%, and 95.4% reported less than 25%. Efforts to prevent resistance included maintaining intervals of over 3 months (54.8%), using products with lower resistance potential (47.0%), employing minimal effective doses (28.2%), and minimizing re-administration (14.9%). CONCLUSION: In the South Korean aesthetic medicine community, a majority of clinical physician's report encountering botulinum toxin resistance. Given the potential loss of various benefits associated with resistance, there is a need to establish appropriate guidelines based on mechanistic studies and current status assessments. Educating clinicians on applicable guidelines is crucial.

The impact of neonatal morbidities on child growth and developmental outcomes in very low birth weight infants: a nationwide cohort study.

Growth in preterm infants has long-term implications for neurodevelopmental outcomes. We aimed to estimate the nationwide growth outcomes from birth to 5 years in infants born under 1500 g and to analyze the effects of major morbidities in preterm infants on growth. In total, 2961 children born in 2013 with a birth weight under 1500 g who underwent an infant health checkup between 2013 and 2018 according to the National Health Insurance Service database were included. Checkups were conducted at 4-6, 9-12, 18-24, 30-36, 42-48, and 54-60 months of age. Information was obtained from the International Classification of Diseases-10 codes or a questionnaire administered during the check-up. At 60 months of age, the mean percentiles of weight, height, and head circumference fell within only the 30-40th percentile of normal growth values. About 30% of infants had growth parameters below the 10th percentile and showed worse neurodevelopmental outcomes. Using multiple logistic regression, infants with bronchopulmonary dysplasia showed a significantly higher incidence of growth restriction in all three categories of weight (odds ratio [OR] 1.50), height (OR 1.33), and head circumference (OR 1.36) at 60 months. Sepsis was associated with growth restriction in weight (OR 1.43) and head circumference (OR 1.33). Periventricular leukomalacia infants had relatively small head circumferences (OR 1.91) and poor developmental screening results (OR 2.89).Conclusion: Catch-up growth remains a major issue in infants born under 1500 g, especially those with some morbidities from preterm birth. Regular checkups to monitor and early intervention to achieve normal growth are essential. What is Known: • Growth in preterm infants has long-term implications for neurodevelopmental and cardiometabolic outcomes. • Data are lacking on the time-serial effects of many preterm morbidities simultaneously on long-term growth outcomes. What is New: • All growth parameters of VLBW infants, including weight, height, and head circumference, fell within the 30-40th percentile of normal growth for infants at 60 months of age, indicating that catch-up growth for VLBW infants remains an issue. • VLBW infants with major preterm morbidities, including BPD, PVL, and sepsis, showed difficulties in achieving normal catch-up growth and neurodevelopment at 60 months of age.

Tools for assessing lung fluid in neonates with respiratory distress.

BACKGROUND: Transient tachypnea of the newborn (TTN), as a common cause of neonatal respiratory distress, needs to be distinguished from respiratory distress syndrome (RDS). Various modalities such as lung ultrasonography, cytokine analysis, and electrical cardiometry for the evaluation of lung fluid can be helpful for the exact diagnosis, however, clinical diagnosis has been applied mainly. This study aimed to evaluate the usefulness of the various tools for the diagnosis of TTN and RDS in neonates. METHODS: This study evaluated 22 late-preterm and term infants admitted to the neonatal intensive care unit of Gangnam Severance Hospital because of respiratory distress. Total 9 neonates were diagnosed with TTN and 13 had RDS. In addition to chest radiography, the LUS score was calculated by a neonatologist using the portable ultrasound device. Cytokines in the bronchoalveolar lavage fluid supernatant were measured. Thoracic fluid content was measured using an electrical cardiometry device. RESULTS: We enrolled 22 patients with median gestational age, 37.1 weeks, and birth weight 3100 g. There is no difference in patient characteristics between RDS and TTN group. Lung ultrasound score was significantly higher in RDS than TTN (11 vs 6, p = 0.001). Score 0 is shown in all infants with TTN. Score 1 is shown as significantly more in RDS than TTN. Between the TTN and RDS groups, there were significant differences in the changes of thoracic fluid content (2 vs - 1.5, p < 0.001), IL-1ß levels (2.5 vs 11.3, p = 0.02), and TNF-α levels (20.1 vs 11.2, p = 0.04). CONCLUSION: We found lung ultrasound and electrical cardiometry to be reliable diagnostic tools for assessing infants with respiratory distress among late-preterm and term infants. Further studies with a large number of patients are needed to confirm their clinical usefulness.

Growth Pattern With Morbidities From Birth to 5 Years of Age in Very Low Birth Weight Infants: Comparison of the Korean National Network and National Health Insurance Service.

BACKGROUND: Long-term growth data of very low birth weight (VLBW) infants are currently collected in the Korean Neonatal Network (KNN) and National Health Insurance Service (NHIS) database. However, variance in the number of infants, check-up time, and check-up parameters led to decreased credibility of cumulated data. We aimed to compare the data on serial growth outcomes by major morbidities from birth to 5 years in VLBW infants between the KNN and NHIS databases. METHODS: We combined the NHIS and KNN data of VLBW infants born between 2013 and 2015. The check-up times in the NHIS database were at 4-6, 9-12, 18-24, 30-36, 42-48, and 54-60 months of age, whereas in the KNN were at 18-24 months of corrected age and at 36 months of age. RESULT: Among 8,864 VLBW infants enrolled based on the birth certificates from the Statistics Korea, 6,086 infants (69%) were enrolled in the KNN, and 5,086 infants (57%) participated in the NHIS health check-up. Among 6,068 infants, 3,428 infants (56%) were enrolled at a corrected age of 18-24 months and 2,572 infants (42%) were enrolled at a chronological age of 33-36 months according to the KNN follow-up registry. However, based on the national birth statistics data, the overall follow-up rate of the KNN at 36 months of age was as low as 29%. The NHIS screening rate was lower at first (23%); however, it increased over time to exceed the KNN follow-up rate. Growth failure (weight under 10th percentile) at corrected ages of 18-24 months and 36 months were more common in the NHIS than KNN (42% vs. 20%, 37% vs. 34.5%). Infants with bronchopulmonary dysplasia and periventricular leukomalacia showed similar rates of growth failure at 2 years but varying rates at 3 years between the KNN and NHIS. CONCLUSION: By integrating the KNN and NHIS data indirectly at continuous time points according to morbidities, we found that there are discontinuities and discrepancies between the two databases among VLBW infants. Establishing an integrated system by patient level linking the KNN and NHIS databases can lead to better understanding and improved neonatal outcomes in VLBW infants in Korea.

Pharmacokinetics and safety of evogliptin in hepatically impaired patients.

AIMS: Evogliptin is a potent and selective dipeptidyl peptidase-4 inhibitor for glycaemic control in patients with type 2 diabetes mellitus. Since evogliptin is mainly eliminated through hepatic metabolism, we investigated the pharmacokinetics (PKs) and safety characteristics of evogliptin in Korean patients with mild or moderate hepatic impairment. METHODS: An open-label, parallel-group study was conducted in patients with mild or moderate hepatic impairment and healthy control subjects matched to each patient for sex, age and body mass index. A single dose (5 mg) of evogliptin was administered orally, and serial blood samples were collected over 120 h to assess the PK profile of evogliptin and its main metabolites (M7 and M8). RESULTS: Patients with mild hepatic impairment and their matched healthy controls showed similar maximum concentration (Cmax ) and area under the concentration-time curve values from 0 to 120 h (AUClast ); the geometric mean ratio (GMR) and 90% confidence interval (CI) were 1.04 (0.80, 1.35) and 1.01 (0.90, 1.14), respectively. Exposure to evogliptin (Cmax and AUClast ) was increased by about 40% in patients with moderate hepatic impairment-the GMR and 90% CI were 1.37 (1.09, 1.72) and 1.44 (1.18, 1.75), respectively. The metabolic ratios of M7 and M8 were lower in patients with moderate hepatic impairment than in matched healthy controls. Evogliptin was well tolerated by both patients and healthy subjects. CONCLUSION: Although evogliptin exposure was increased in patients with moderate hepatic impairment, the increase is unlikely to affect safety and efficacy adversely, and no dose adjustment is warranted.

Outcomes of infants born to pregnant women with syphilis: a nationwide study in Korea.

BACKGROUND: Despite the expansion of antenatal syphilis screening programs, congenital syphilis (CS) remains a concern. PURPOSE: This study aimed to analyze the manifestation and progress of CS, including treatment and follow-up, based on a nationwide study. METHODS: From the Korean National Health Insurance Service database, a total of 548 infants were examined for CS during their first year of life from 2013 to 2018. Neurosyphilis and complications were investigated using the International Classification of Diseases-10 codes. RESULTS: The birth rate of infants from mothers with syphilis was 2.8 per 10,000 live births for 5 years, which is not indicative of a decreasing trend. Overall, 148 infants were proven or highly probable or possible of having CS with treatment for 10 days; 66 infants were possible or less likely of having CS with only 1-day treatment. Jaundice (56 %) was common, followed by hearing impairment (14 %), renal disease (8 %), and mental retardation (8 %). Fourteen cases of neurosyphilis occurred. Infants with complications, including mental retardation, eye involvement, hearing impairment, or renal disease, were significantly associated with neurosyphilis (OR 8.49, P < 0.0001). Of 250 patients who received treatment, 92.8 % were treated with one medication: benzathine penicillin was used in 73 % of patients. Only four patients were re-treated due to treatment failure. In addition to the treponemal test, fluorescent treponemal antibody-absorption was the most utilized tool for diagnosis and follow-up. CONCLUSIONS: Establishing standardized guidelines for the evaluation of CS, as well as the establishment of treatment regimens and follow up-plans for the disease, at a national level would help improve maternal and neonatal care and facilitate the eradication of CS in Korea.

Epidemiology of Macrosomia in Korea: Growth and Development.

BACKGROUND: Macrosomia, as an infant with birth weight over 4 kg, can have several perinatal, and neonatal complications. This study aimed to estimate the incidence of macrosomia in Korea and to identify the growth and developmental outcomes and other neonatal complications. METHODS: In total, 397,203 infants who were born in 2013 with birth weight ≥ 2.5 kg and who underwent infant health check-up between their 1st and 7th visit were included from the National Health Insurance Service database. The information was obtained by the International Classification of Diseases-10 codes or self-reported questionnaires in the National Health Screening Program. RESULTS: The distribution of infants by birth weight was as follows: 384,181 (97%) infants in the 2.5-3.99 kg (reference) group, 12,016 (3%) infants in the 4.0-4.49 kg group, 772 (0.2%) infants in the 4.5-4.99 kg group, and 78 (0.02%) infants in the ≥ 5 kg group. Macrosomia showed significantly higher incidence of sepsis, male sex, and mothers with GDM and birth injury. There was a significant difference in weight, height, and head circumference according to age, birth weight group, and combination of age and birth weight, respectively (P < 0.001). The number of infants with the weight above the 90th percentile in macrosomia at each health check-up showed higher incidence than in reference group. The mean body mass index significantly differed among the groups, as 50.6 in infants with 2.5-3.99 kg of birth weight, 63.5 with 4.0-4.49 kg, 71.0 with 4.5-4.99 kg, and 73.1 with ≥ 5 kg. There was a significant difference in the incidence of poor developmental results between infants with macrosomia and the reference group at 24, 36 and 48 month of age. CONCLUSION: Macrosomia was significantly associated with the risk of sepsis, birth injury, obesity and developmental problem especially in a boy born from mothers with gestational diabetes mellitus. Careful monitoring and proper strategies for monitoring growth and development are needed.

Efficacy of Lenvervimab, a Recombinant Human Immunoglobulin, in Treatment of Chronic Hepatitis B Virus Infection.

The mechanism of action of hepatitis B immunoglobulin (HBIG) for chronic hepatitis B (CHB) treatment is not fully understood. A clinical trial in Japan suggested that HBIG therapy might benefit patients with CHB.1 Lenvervimab, a recombinant monoclonal HBIG developed by GC Pharma (Yongin, South Korea), has been screened from an anti-HBs-enriched phage-display library cloned from hepatitis B vaccine-boosted human blood cells and was produced in Chinese hamster ovary cells.2-4.

Pulmonary Surfactant Replacement Therapy for Respiratory Distress Syndrome in Neonates: a Nationwide Epidemiological Study in Korea.

BACKGROUND: Pulmonary surfactant (PS) replacement therapy, as a safe and effective treatment for respiratory distress syndrome (RDS) may have further increased with the extended insurance coverage since 2011 in Korea. Thus, this study aimed to investigate the epidemiologic data of PS replacement therapy for RDS in Korea and to analyze the complications associated with RDS. METHODS: We included 19,442 infants who were treated with PS and diagnosed with RDS (International Classification of Diseases-10 codes: P22.0) between 2014 and 2018 from the Health Insurance Review and Assessment database. Birth certificate data from Statistics Korea were used to estimate the incidence of RDS. RESULTS: The average incidence of RDS within the study period was 0.99% among live births. Repeated doses of PS were administered to 1,688 infants (8.7%), ranging from 2 doses in 929 infants (4.8%) to 9 doses in 1 infant (0.01%). The incidence of RDS in term infants markedly increased over 5 years from 0.2% to 0.34%. The incidence was similarly increased among the preterm infants. The RDS mortality rate was 6.3% and showed a decreasing trend according to year. The mortality rate was significantly higher in the lower gestational age group. A decreasing trend was observed in the incidence of the complications, such as patent ductus arteriosus, intraventricular hemorrhage, and bronchopulmonary dysplasia, except for pneumothorax in term infants. The complications were also higher in the lower gestational age group and the lower birth weight group. However, pneumothorax was the most frequent complication in the term infant group and in infants with birth weight ≥ 2,500 g. CONCLUSION: Advancements in neonatal care and extended insurance coverage have increased the use of PS replacement therapy for RDS. This, in turn, decreased neonatal mortality and the incidence of the associated complications. The appropriate therapeutic strategy for RDS should be decided according to the gestational age and lung pathology.

Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy.

BACKGROUND: Sufentanil is commonly used for analgesia and sedation during extracorporeal membrane oxygenation (ECMO). Both ECMO and the pathophysiological changes derived from critical illness have significant effects on the pharmacokinetics (PK) of drugs, yet reports of ECMO and sufentanil PK are scarce. Here, we aimed to develop a population PK model of sufentanil in ECMO patients and to suggest dosing recommendations. METHODS: This prospective cohort PK study included 20 patients who received sufentanil during venoarterial ECMO (VA-ECMO). Blood samples were collected for 96 h during infusion and 72 h after cessation of sufentanil. A population PK model was developed using nonlinear mixed effects modelling. Monte Carlo simulations were performed using the final PK parameters with two typical doses. RESULTS: A two-compartment model best described the PK of sufentanil. In our final model, increased volume of distribution and decreased values for clearance were reported compared with previous PK data from non-ECMO patients. Covariate analysis showed that body temperature and total plasma protein level correlated positively with systemic clearance (CL) and peripheral volume of distribution (V2), respectively, and improved the model. The parameter estimates of the final model were as follows: CL = 37.8 × EXP (0.207 × (temperature - 36.9)) L h-1, central volume of distribution (V1) = 229 L, V2 = 1640 × (total plasma protein/4.5)2.46 L, and intercompartmental clearance (Q) = 41 L h-1. Based on Monte Carlo simulation results, an infusion of 17.5 µg h-1 seems to reach target sufentanil concentration (0.3-0.6 µg L-1) in most ECMO patients except hypothermic patients (33 °C). In hypothermic patients, over-sedation, which could induce respiratory depression, needs to be monitored especially when their total plasma protein level is low. CONCLUSIONS: This is the first report on a population PK model of sufentanil in ECMO patients. Our results suggest that close monitoring of the body temperature and total plasma protein level is crucial in ECMO patients who receive sufentanil to provide effective analgesia and sedation and promote recovery. TRIAL REGISTRATION: Clinicaltrials.gov NCT02581280 , December 1st, 2014.

Pharmacokinetics and safety of transdermal and oral granisetron in healthy Chinese subjects: An open-label, randomized, crossover study
.

AIMS: To examine the pharmacokinetics and safety of granisetron during transdermal delivery and oral administration to healthy Chinese male subjects. MATERIALS AND METHODS: A single 34.3 mg/52 cm2 transdermal delivery patch of granisetron and the 1-mg tablet of granisetron were dosed to subjects in an open-label, randomized, crossover study. Two dosing schemes were established: scheme 1, in which the 5-day oral administration phase of the tablet (the OA phase) (twice daily every 12 hours) was conducted, followed by the 6-day transdermal delivery phase of the patch (the TD phase); and scheme 2, in which these two phases were conducted in reverse order. Plasma concentrations of granisetron were measured according to high-performance liquid chromatography, and the following pharmacokinetic parameters were determined: Cavg [AUC0-24,ss (day 5)/24 for OA and AUC24-144/120 for TD], Cmax, tmax, AUC, and T1/2. RESULTS: All of the subjects completed the TD phase, and 1 subject withdrew from the study due to increased alanine aminotransferase. The Cavg values for OA and TD were 2.95 ± 1.60 ng/mL and 2.83 ± 1.43 ng/mL, respectively. The Cmax values at steady state for OA and TD were 5.98 ± 2.27 ng/mL and 3.91 ± 2.23 ng/mL, respectively. The incidences of adverse events (AEs) possibly or definitely related to OA and TD were 45.83% and 37.5%, respectively. No serious AEs were found in the two dosing schemes. CONCLUSION: The Cavg values determined through TD and OA were equivalent, indicating similar drug exposures. Therefore, the granisetron patch may be an alternative formulation for oral granisetron in Chinese individuals.
.

USP14 Inhibition Regulates Tumorigenesis by Inducing Autophagy in Lung Cancer In Vitro.

The ubiquitin-proteasome system is an essential regulator of several cellular pathways involving oncogenes. Deubiquitination negatively regulates target proteins or substrates linked to both hereditary and sporadic forms of cancer. The deubiquitinating enzyme ubiquitin-specific protease 14 (USP14) is associated with proteasomes where it trims the ubiquitin chain on the substrate. Here, we found that USP14 is highly expressed in patients with lung cancer. We also demonstrated that USP14 inhibitors (IU1-47 and siRNA-USP14) significantly decreased cell proliferation, migration, and invasion in lung cancer. Remarkably, we found that USP14 negatively regulates lung tumorigenesis not only through apoptosis but also through the autophagy pathway. Our findings suggest that USP14 plays a crucial role in lung tumorigenesis and that USP14 inhibitors are potent drugs in lung cancer treatment.

Pharmacokinetic drug interaction and safety after coadministration of clarithromycin, amoxicillin, and ilaprazole: a randomised, open-label, one-way crossover, two parallel sequences study.

PURPOSE: Ilaprazole, the latest proton pump inhibitor, can be used with clarithromycin and amoxicillin as a triple therapy regimen for eradicating Helicobacter pylori. The aim of this study was to evaluate pharmacokinetic drug interactions and safety profiles after coadministration of clarithromycin, amoxicillin, and ilaprazole. METHODS: A randomised, open-label, one-way crossover, two parallel sequences study was conducted in 32 healthy subjects. In part 1, the subjects received a single dose of ilaprazole 10 mg in period 1 and clarithromycin 500 mg and amoxicillin 1000 mg twice daily for 6 days in period 2. In part 2, the subjects received clarithromycin 500 mg and amoxicillin 1000 mg once in period 1 and ilaprazole 10 mg twice daily for 6 days in period 2. In both sequences, the three drugs were coadministrated once on day 5 in period 2. Pharmacokinetic evaluations of ilaprazole (part 1), and clarithromycin and amoxicillin (part 2) were conducted. RESULTS: Twenty-eight subjects completed the study. For ilaprazole, the peak concentration (Cmax) slightly decreased from 479 (ilaprazole alone) to 446 ng/mL (triple therapy) [Geometric least square mean ratio (90% confidence interval), 0.93 (0.70-1.22)]. The area under the concentration-time curve from 0 h to the last measurable concentration (AUClast) slightly increased from 3301 to 3538 µg·h/mL [1.07 (0.85-1.35)]. For clarithromycin, the Cmax slightly decreased from 1.87 to 1.72 µg/mL [0.90 (0.70-1.15)], and AUClast slightly increased from 14.6 to 16.5 µg·h/mL [1.09 (0.87-1.37)]. For amoxicillin, the Cmax slightly decreased from 9.37 to 8.14 µg/mL [0.86 (0.74-1.01)], and AUClast slightly decreased from 27.9 to 26.7 µg·h/mL [0.98 (0.83-1.16)]. These changes in the PK parameters of each drug were not statistically significant. CONCLUSIONS: The coadministration of ilaprazole, clarithromycin, and amoxicillin was tolerable and did not cause a significant PK drug interaction. Thus, a triple therapy regimen comprising ilaprazole, clarithromycin, and amoxicillin may be an option for the eradication of H. pylori. Clinicaltrials.gov number: NCT02998437.

Population pharmacokinetic model of levetiracetam in Korean neonates with seizures
.

OBJECTIVE: This study was conducted to develop a population pharmacokinetic (PK) model of levetiracetam in Korean neonates with seizures. MATERIALS AND METHODS: Data were obtained from a retrospective study of 18 neonates with seizures admitted to the Neonatal Intensive Care Unit (NICU) of Severance Children's Hospital for the period of from 2013 to 2015. Sampling and dosing times were recorded by clinical research coordinators on case report forms. Demographic factors and laboratory results were tested as potential covariates for PK parameters. Model development was performed within a mixed-effect modeling framework using NONMEM. RESULTS: With a one-compartment model with first-order elimination chosen as a basic PK model based on theory-based allometric relationships, postmenstrual age and serum creatinine were found to have significant influences on clearance (CL). Typical parameter estimates of the final PK model obtained, evaluated at covariate medians, were 1.08 L/kg for volume of distribution (V) and 0.073 L/h/kg (= 1.23 mL/min/kg) for CL, illustrating that V in Korean neonates is a little larger than in Western population while CL is similar. CONCLUSION: A population PK model of levetiracetam for Korean neonates with seizures was developed in this study. The result of this study can be used as a basis to develop an optimal dosage regimen in Korean neonates with seizures.
.

Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation.

The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a >50% probability of target attainment at 72 h using a trough concentration target of >10 µg/ml for mild to moderate infections and a trough concentration target of >15 µg/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.).

Abnormal neurodevelopmental outcomes are very likely in cases of bilateral neonatal arterial ischaemic stroke.

AIM: Neonatal arterial ischaemic stroke (AIS) is an important cause of severe neurological disability. This study aimed to analyse the clinical manifestations and outcomes of AIS patients. METHODS: We enrolled neonates with AIS admitted to Severance Children's Hospital and Gangnam Severance Hospital between 2008 and 2015. AIS was confirmed using magnetic resonance imaging (MRI). We retrospectively reviewed the clinical manifestations, MRI findings, electroencephalography (EEG) findings and neurodevelopmental outcomes. RESULTS: The study comprised 29 neonates (18 boys). The mean follow-up period was 15.4 months (range 6-44 months), and the mean age at diagnosis was 8.1 days. Seizure was the most common symptom (66%). Bilateral involvement was more common than unilateral involvement (52%). The middle cerebral artery was the most commonly identified territory (79%). Abnormal EEG findings were noted in 93% of the cases. Neurodevelopment was normal in 11 (38%) patients, while cerebral palsy and delayed development were noted in eight (28%) and six (21%) patients, respectively. Patients with bilateral involvement were very likely to have abnormal neurodevelopmental outcomes. CONCLUSION: Our study showed that abnormal neurodevelopmental outcomes were very likely after cases of neonatal AIS with bilateral involvement, and clinicians should consider early and more effective interventions in such cases.

Using the Endoscopic Transconjunctival and Transcaruncular Approach to Repair Combined Orbital Floor and Medial Wall Blowout Fractures.

PURPOSE: To demonstrate the effectiveness of the endoscopic transcaruncular and transconjunctival approach in the repair of combined medial and inferior orbital wall fractures. METHODS: A retrospective chart review was conducted on 160 patients with combined medial and inferior orbital wall fractures. All patients underwent surgery via an endoscopic transcaruncular and transconjunctival approach without lateral canthotomy, performed by a single surgeon. Porous polyethylene sheets (1.0 mm in thickness) were implanted to cover the orbital defects. The minimal postoperative follow-up period was 6 months. The authors evaluated enophthalmos, diplopia, and ocular motility pre and postoperatively and report surgical complications. RESULTS: A total of 160 patients were included, comprising 121 men and 39 women. The mean patient age was 33.9 ±â€Š14.1 years, and the mean postoperative follow-up period was 12 months. The average enophthalmos was 3.20 mm preoperatively, and the mean improvement at 6 months after surgery was 2.82 mm. One patient suffered a canalicular laceration after surgery, and another retrobulbar hemorrhage; however, both of these complications resolved with appropriate management. Otherwise, there were no significant surgical complications including newly developed diplopia, decreased visual acuity, or cerebrospinal fluid leakage. CONCLUSIONS: The endoscopic transcaruncular and transconjunctival approach is a useful and promising technique to repair combined medial and inferior orbital wall fractures.

A low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminium garnet laser for the treatment of café-au-lait macules.

BACKGROUND: Café-au-lait macules (CALMs) are a common pigmentary disorder. Although a variety of laser modalities have been used to treat CALMs, their efficacies vary and dyspigmentation may develop. OBJECTIVE: We evaluated the clinical efficacy and safety of a low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminium garnet (Nd:YAG) laser for the treatment of CALMs. METHODS: In a preliminary investigation, 6 patients underwent a split-lesion comparative study with 532- and 1064-nm Q-switched Nd:YAG laser treatment. In total, 32 patients with 39 CALMs were enrolled in a subsequent prospective trial to evaluate the treatment with a low-fluence 1064-nm Q-switched Nd:YAG laser. RESULTS: In the preliminary study, the 1064-nm treatment group had a more favorable response and a shorter recovery time. In a subsequent prospective trial of a 1064-nm laser, 74.4% of the lesions showed a clinical response with clearance of ≥50.0%. The treatment regimen was well tolerated; 15.4% of patients experienced adverse events. LIMITATIONS: The study participants were followed for 6 months, and there were no relevant treatment controls in the prospective trial group. CONCLUSION: Low-fluence 1064-nm Q-switched Nd:YAG laser therapy afforded good clinical improvement for treating CALMs.

Cystic adventitial disease of the common femoral artery at a previous surgical dissection site.

Cystic adventitial disease (CAD) is a rare vascular disorder associated with nonatherosclerotic peripheral vessel disease and occurs when mucoid cysts in the adventitia compress the blood vessel. The underlying etiology and pathogenesis of CAD remain debatable as various theories have been suggested. This case is interesting because the cyst developed from the previous common femoral artery (CFA) dissection site. To our knowledge, this is the first report of CAD developed at a previous operation site. Thus, we report herein a case of CAD arising from a previous embolectomy dissection site in the CFA that was successfully treated with surgery.

Population pharmacokinetic-pharmacodynamic modeling of clopidogrel for dose regimen optimization based on CYP2C19 phenotypes: A proof of concept study.

Clopidogrel is an antiplatelet drug used to reduce the risk of acute coronary syndrome and stroke. It is converted by CYP2C19 to its active metabolite; therefore, poor metabolizers (PMs) of CYP2C19 exhibit diminished antiplatelet effects. Herein, we conducted a proof-of-concept study for using population pharmacokinetic-pharmacodynamic (PK-PD) modeling to recommend a personalized clopidogrel dosing regimen for individuals with varying CYP2C19 phenotypes and baseline P2Y12 reaction unit (PRU) levels. Data from a prospective phase I clinical trial involving 36 healthy male participants were used to develop the population PK-PD model predicting the concentrations of clopidogrel, clopidogrel H4, and clopidogrel carboxylic acid, and linking clopidogrel H4 concentrations to changes in PRU levels. A two-compartment model effectively described the PKs of both clopidogrel and clopidogrel carboxylic acid, and a one-compartment model of those of clopidogrel H4. The CYP2C19 phenotype was identified as a significant covariate influencing the metabolic conversion of the parent drug to its metabolites. A PD submodel of clopidogrel H4 that stimulated the fractional turnover rate of PRU levels showed the best performance. Monte Carlo simulations suggested that PMs require three to four times higher doses than extensive metabolizers to reach the target PRU level. Individuals within the top 20th percentile of baseline PRU levels were shown to require 2.5-3 times higher doses than those in the bottom 20th percentile. We successfully developed a population PK-PD model for clopidogrel considering the impact of CYP2C19 phenotypes and baseline PRU levels. Further studies are necessary to confirm actual dosing recommendations for clopidogrel.