The comprehensive in vitro proarrhythmia assay (CiPA) initiative, led by the U.S. Food and Drug Administration (FDA), provides a framework for predicting drug-induced arrhythmia risk. To support domestic CiPA implementation, we evaluated the proarrhythmic risk of sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor. Sildenafil has been misused recreationally, with reports of highdose non-medical intake. To simulate misuse, in vitro assays were conducted using concentrations up to 100× the maximum therapeutic plasma concentration (Cmax). The assessment followed the three core components of the CiPA paradigm. Patch clamp assays were conducted in Human Embryonic Kidney 293 (HEK293) and Chinese hamster ovary (CHO) cells transiently expressing Nav1.5, Cav1.2, and hERG ion channels. In silico modeling was performed using the CiPAORdv1.0 model based on IC₅₀ and Hill coefficient values. Functional evaluation included multi-electrode array (MEA) recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and in vivo electrocardiography (ECG) analysis in rats was performed to observe QT interval prolongation. Sildenafil significantly inhibited hERG currents by 40.5% at 100× Cmax. In silico modeling predicted a low Torsades de Pointes (TdP) risk based on qNet biomarkers. In contrast, MEA recordings showed a concentration-dependent prolongation of corrected field potential duration (FPDc), with a significant 13.3% increase at 100× Cmax. The TdP risk estimated from MEA modeling was 64%. In vivo ECG analysis revealed significant QT prolongation at 50× Cmax. Despite low in silico TdP predictions, functional assays suggest that high concentrations of sildenafil as in misuse may pose a clinically relevant risk of QT prolongation and arrhythmia.

Objective: To compare the convenience and effectiveness of the existing lumbosacral orthoses (LSO) (classic LSO and Cybertech) and a newly developed LSO (V-LSO) by analyzing postoperative data. Methods: This prospective cohort study was performed from May 2019 to November 2019 and enrolled and analyzed 88 patients with degenerative lumbar spine disease scheduled for elective lumbar surgery. Three types of LSO that were provided according to the time of patient registration were applied for 6 weeks. Patients were randomized into the classic LSO group (n=31), Cybertech group (n=26), and V-LSO group (n=31). All patients were assessed using the Oswestry Disability Index (ODI) preoperatively and underwent plain lumbar radiography (anteroposterior and lateral views) 10 days postoperatively. Lumbar lordosis (LS angle) and frontal imbalance were measured with and without LSO. At the sixth postoperative week, a follow-up assessment with the ODI and orthosis questionnaire was conducted. Results: No significant differences were found among the three groups in terms of the LS angle, frontal imbalance, ODI, and orthosis questionnaire results. When the change in the LS angle and frontal imbalance toward the reference value was defined as a positive change with and without LSO, the rate of positive change was significantly different in the V-LSO group (LS angle: 41.94% vs. 61.54% vs. 83.87%; p=0.003). Conclusion The newly developed LSO showed no difference regarding its effectiveness and compliance when compared with the existing LSO, but it was more effective in correcting lumbar lordosis.

PURPOSE: We sought to evaluate the distribution and characteristics of meibomian gland dysfunction (MGD) and the treatment patterns for symptomatic MGD patients in South Korea. METHODS: One hundred ninety-six right eyes of 196 MGD patients were enrolled. For each patient, meibum expressibility in the central eight glands in both the upper and lower eyelids was examined. Each upper and lower eyelid was separately classified into one of the following three subtypes: nonobvious obstructive (low-delivery without lid margin abnormality), obvious obstructive (low-delivery with lid margin abnormality), and hypersecretory (high-delivery with lid margin abnormality). All treatment plans were also recorded. RESULTS: The mean number of expressible glands of the central eight glands in the upper eyelids (3.9 ± 2.6) was significantly higher than that in the lower eyelids (2.2 ± 2.4, p < 0.001). Obvious obstructive MGD was the most common subtype, followed by the hypersecretory and nonobvious obstructive subtypes in both the upper and lower eyelids. Of the 196 subjects, 38 (19.4%) had upper and lower eyelids that were assigned to different categories. Eyelid hygiene was the most prescribed treatment (74.5%), followed by lubricant eye drop usage (71.5%). Physicians tended to determine treatment plans based on the subtype of the upper eyelid rather than that of the lower eyelid. CONCLUSIONS: The majority of subjects were classified as having the obvious obstructive subtype of MGD, and 19.4% had upper and lower eyelids that were different subtypes. Eyelid hygiene was the most prescribed treatment for MGD patients, and treatment patterns were mostly determined based on the subtype of the upper eyelids.
Classification ; Diagnosis ; Eyelids ; Humans ; Hygiene ; Korea ; Meibomian Glands

Carbon dioxide (CO2) laser is one of the most widely used lasers in dermatology. CO2 laser can precisely ablate the skin with good hemostasis, which makes it an ideal surgical laser. With the development of pulsed CO2 laser, which enabled cleaner ablation with less residual thermal damage, CO2 laser resurfacing became the gold standard for skin rejuvenation. The rejuvenation effect of full-face CO2 laser resurfacing is unparalleled to other methods; however, it is associated with a relative high incidence of side effects and prolonged downtime. Fractional CO2 laser was developed to overcome this problem. With a new technology of fractionating the laser beam into hundreds of microbeams, fractional CO2 laser resurfacing can improve various skin conditions including skin laxity, photodamage, and acne scars with short downtime and significantly lesser side effects. For optimal treatment results, clinicians have to decide the treatment depth and density based on proper understanding of the laser tissue interaction and underlying skin conditions.
Acne Vulgaris ; Carbon Dioxide* ; Carbon* ; Cicatrix ; Dermatology ; Hemostasis ; Incidence ; Lasers, Gas* ; Rejuvenation ; Skin

No abstract available.
Alagille Syndrome* ; Cholestasis ; Xanthomatosis*

PURPOSE: High sensitive C-reactive protein (hs CRP) is well known as a strong risk factor of cardiovascular disease (CVD). The aim of this study is to evaluate the impact of elevated hs CRP on coronary artery spasm (CAS) as assessed by intracoronary acetylcholine (ACh) provocation test. MATERIALS AND METHODS: A total of 1729 consecutive patients without significant CVD who underwent coronary angiography and intracoronary ACh test between November 2004 and August 2010 were analyzed. The patients were divided into five groups according to quintiles of hs CRP levels. RESULTS: At baseline, the prevalence of elderly, hypertension, diabetes mellitus, current smoking, and lipid levels were higher in patients with higher hs CRP. During ACh test, the incidences of significant CAS, ischemic electrocardiography (EKG) change, multivessel, and diffuse CAS were higher in patients with higher hs CRP. Multivariate analysis showed that the old age (OR=1.01, CI; 1.0-1.02, p=0.0226), myocardial bridge (OR=3.34, CI; 2.16-5.17, p<0.001), and highest quintile hs CRP (OR=1.54, CI; 1.12-2.18, p=0.008) were independent predictors of ACh induced CAS. However, there was no difference in clinical outcomes up to 12 months. CONCLUSION: In conclusion, higher hs CRP was associated with higher incidence of CAS, worse angiographic characteristics and ischemic EKG change, but was not associated with clinical outcomes.
Acetylcholine/*metabolism ; Adult ; C-Reactive Protein/*metabolism ; Coronary Vasospasm/*metabolism ; Diabetes Mellitus/metabolism ; Female ; Humans ; Hypertension/metabolism ; Male ; Middle Aged ; Retrospective Studies

PURPOSE: Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease of unknown etiology. The diagnosis of IGM requires that other granulomatous lesions in the breast be excluded. Tuberculous mastitis (TM) is also an uncommon disease that is often difficult to differentiate from IGM. The purpose of this study is to develop a new algorithm for the differential diagnosis and treatment of IGM and TM. METHODS: Medical records of 68 patients (58 with IGM and 10 with TM) between July 1999 and February 2009 were retrospectively reviewed. RESULTS: The mean age of the patients was 33.5 (IGM) and 40 (TM) years (p=0.018). The median follow-up was 84 months. Of the total 10 patients with TM, 5 patients had a history of pulmonary tuberculosis. The most common symptoms of the diseases were breast lump and pain. However, axillary lymphadenopathy was more seen in TM (50%) compared to IGM (20.6%) (p=0.048). TM showed more cancer-mimicking findings on radiologic study (p=0.028). In IGM, 48 patients (82.7%) underwent surgical wide excision and 21 patients (36.2%) were managed with corticosteroid therapy and antibiotics. All of the TM patients received anti-tuberculosis medications and 9 patients (90%) underwent wide excision. The mean treatment duration was 2.8 months in IGM and 8.4 months in TM. Recurrence developed in 5 patients (8.6%) in IGM and 1 patient (10%) in TM. CONCLUSION: This study shows different characteristics between IGM and TM. The IGM patients were younger and had more mastalgia symptoms than the TM patients. Axillary lymphadenopathy was seen more often in TM patients. Half of the TM patients had pulmonary tuberculosis or tuberculosis lymphadenitis. Surgical wide excision might be both therapeutic and useful for providing an exact diagnosis.
Anti-Bacterial Agents ; Breast ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Granulomatous Mastitis ; Humans ; Immunoglobulin M ; Lymphadenitis ; Lymphatic Diseases ; Mastitis ; Mastodynia ; Medical Records ; Recurrence ; Retrospective Studies ; Tuberculosis ; Tuberculosis, Pulmonary

PURPOSE: To evaluate the complication incidence of 23-gauge pars plana vitrectomy day surgery. METHODS: A retrospective review was conducted on 79 eyes that underwent 23-gauge pars plana vitrectomy day surgery from September 2009 to September 2010. The main outcome measures included changes in best corrected visual acuity (BCVA), intraocular pressure (IOP), and presence of postoperative complications after the day surgery. RESULTS: The mean preoperative log MAR BCVA improved from 1.32 +/- 0.96 to 0.40 +/- 0.41 at 3 months after surgery (p < 0.05). There was no significant differences between the mean preoperative IOP and IOP on the 1st day after surgery (p > 0.05). At the end of surgery, suture placement was required for sclerotomy site leakage in 4 eyes (5.1%). There were 10 eyes (12.7%) with postoperative complications, including 7 eyes with increased IOP (8.9%), hypotony in 2 eyes (2.6%) and vitreous hemorrhage in 1 eye (1.3%), with no case requiring reoperation. CONCLUSIONS: The patients who underwent 23-gauge pars plana vitrectomy day surgery achieved visual improvement without serious complications postoperatively.
Ambulatory Surgical Procedures ; Eye ; Humans ; Incidence ; Intraocular Pressure ; Outcome Assessment (Health Care) ; Postoperative Complications ; Retrospective Studies ; Sutures ; Visual Acuity ; Vitrectomy ; Vitreous Hemorrhage