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This article discusses the development of topical therapeutics for the treatment of UV-induced skin hyperpigmentary disorders. The researchers used a screening tool to identify compounds that inhibit melanogenesis, the process of melanin synthesis. They engineered small-molecule analogues of a compound called altiratinib, which showed dose-dependent inhibitory action on melanogenesis but had cytotoxicity at higher concentrations. The researchers designed new compounds that demonstrated comparable or better efficacy in reducing melanin content without cytotoxicity. These compounds also showed enhanced skin permeability and were effective in reducing melanin content in mouse and human skin cultures. The findings suggest that these compounds have the potential to be developed into safe and potent topicals for the treatment of hyperpigmentary diseases. [Extracted from the article]

Anti-reflux surgery (ARS) is an efficient treatment option for gastroesophageal reflux disease (GERD). Despite growing evidence of the efficacy and safety of ARS, medications including proton pump inhibitors (PPIs) remain the most commonly administered treatments for GERD. Meanwhile, ARS can be an effective treatment option for patients who need medications continuously or for those who are refractory to PPI treatment, if proper candidates are selected. However, in practice, ARS is often regarded as a last resort for patients who are unresponsive to PPIs. Accumulating ARS-related studies indicate that surgery is equivalent to or better than medical treatment for controlling typical and atypical GERD symptoms. Furthermore, because of overall reduced medication expenses, ARS may be more cost-effective than PPI. Patients are selected for ARS based on endoscopic findings, esophageal acid exposure time, and PPI responsiveness. Although there is limited evidence, ARS may be expanded to include patients with normal acid exposure, such as those with reflux hypersensitivity. Additionally, other factors such as age, body mass index, and comorbidities are known to affect ARS outcomes; and such factors should be considered. Nissen fundoplication or partial fundoplication including Dor fundoplication and Toupet fundoplication can be chosen, depending on whether the patient prioritizes symptom improvement or minimizing postoperative symptoms such as dysphagia. Furthermore, efforts to reduce and manage postoperative complications and create awareness of the long-term efficacy and safety of the ARS are recommended, as well as adequate training programs for new surgeons. [ABSTRACT FROM AUTHOR]

Mitochondria are double-membrane organelles that play a role in ATP synthesis, calcium homeostasis, oxidation-reduction status, apoptosis, and inflammation. Several human disorders have been linked to mitochondrial dysfunction. It has been found that traditional therapeutic herbs are effective on alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) which are leading causes of liver cirrhosis and hepatocellular carcinoma. The generation of reactive oxygen species (ROS) in response to oxidative stress is caused by mitochondrial dysfunction and is considered critical for treatment. The role of oxidative stress, lipid toxicity, and inflammation in NAFLD are well known. NAFLD is a chronic liver disease that commonly progresses to cirrhosis and chronic liver disease, and people with obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension are at a higher risk of developing NAFLD. NAFLD is associated with a number of pathological factors, including insulin resistance, lipid metabolic dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. As a result, the improvement in steatosis and inflammation is enough to entice researchers to look into liver disease treatment. However, antioxidant treatment has not been very effective for liver disease. Additionally, it has been suggested that the beneficial effects of herbal medicines on immunity and inflammation are governed by various mechanisms for lipid metabolism and inflammation control. This review provided a summary of research on herbal medicines for the therapeutic implementation of mitochondria-mediated ROS production in liver disease as well as clinical applications through herbal medicine. In addition, the pathophysiology of common liver disorders such as ALD and NAFLD would be investigated in the role that mitochondria play in the process to open new therapeutic avenues in the management of patients with liver disease. [ABSTRACT FROM AUTHOR]

Plants contain underutilized resources of compounds that can be employed to combat viral diseases. Aloe vera (L.) Burm. f. (syn. Aloe barbadensis Mill.) has a long history of use in traditional medicine, and A. vera extracts have been reported to possess a huge breadth of pharmacological activities. Here, we discuss the potential of A. vera compounds as antivirals and immunomodulators for the treatment of viral diseases. In particular, we highlight the use of aloe emodin and acemannan as lead compounds that should be considered for further development in the management and prevention of viral diseases. Given the immunomodulatory capacity of A. vera compounds, especially those found in Aloe gel, we also put forward the idea that these compounds should be considered as adjuvants for viral vaccines. Lastly, we present some of the current limitations to the clinical applications of compounds from Aloe, especially from A. vera. [ABSTRACT FROM AUTHOR]

Preoperative diagnosis of prolactinomas is critical because dopamine agonists have been regarded as a primary treatment. However, serum prolactin level alone is suboptimal for differentiating prolactinomas from hyperprolactinemia-causing non-functioning pituitary adenomas (NFPAs). By using the tumor size, the authors tried to investigate an effective parameter for the discrimination. We performed a retrospective review of patients who underwent trans-sphenoidal surgery for pituitary lesions in a single institute between January 2015 and May 2021. Using receiver operating curve (ROC) analyses, we compared performances of serum prolactin levels (PRL), a ratio of serum PRL levels to maximal tumor diameter (MD) (PRL/MD; PDR1), and MD squared (PRL/[MD]2; PDR2) in preoperative diagnosis of prolactinomas. A total of 223 patients with NFPAs (n = 175) and prolactinomas (n = 48) were included in the analysis. A moderate correlation was found between serum prolactin levels and MDs in prolactinomas (Pearson's r prl = 0.43, P = 0.002), whereas a weak correlation was observed in NFPAs (Pearson's r nfpa = 0.17, P = 0.028). Among diagnostic parameters, PDR2 exhibited the optimal diagnostic performance with the cutoff value of 0.83 [㎍/L]/mm2 (area under the curve [AUC] = 0.945), compared with the PDR1 (8.93 [㎍/L]/mm with AUC 0.938) and PRL (99.4 ㎍/L with AUC 0.910). In the external validation study, PDR2 maintained superior performance over PDR1 and PRL (accuracy of 94.8%, 91.8%, and 75.8%, respectively). PDR2 was a more effective indicator than prolactin alone in the preoperative differential diagnosis of prolactinomas and NFPAs, which may help select patients who need medical treatment first. [ABSTRACT FROM AUTHOR]

A novel photopneumatic (PPX) technology, combining blue light-emitting diode (LED) and broadband intense pulsed light (IPL) with vacuum pressure, was developed for the treatment of acne vulgaris (AV). In this study, we enrolled 50 patients with mild to moderate AV. Five successive treatments were performed on one side of the face with a combined PPX device, and the opposite side was treated with only IPL with the same fluences at 2-week intervals. Clinical improvement was evaluated by inflammatory and non-inflammatory acne lesion counts. Additionally, patient self-assessment scores were assessed. The results showed that inflammatory and non-inflammatory acne lesion counts were significantly improved on both sides of the face after treatment (p <.001, p =.001, respectively). Both inflammatory and non-inflammatory lesion counts were significantly reduced on the side treated with PPX when compared to the side treated with IPL alone (p =.008, p =.045, respectively). Thirty-eight of 44 patients reported slight to moderate improvement on the patient self-assessment score. No significant side effect was observed during the study periods.In conclusion, PPX therapy is an effective and safe modality to treat mild to moderate AV. This study shows that PPX therapy has superior efficacy for the treatment of AV compared to IPL monotherapy. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the efficacy and safety of a 3-day aprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) during the first cycle of non-anthracycline plus cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) based on government guidelines in Korean patients.Methods: This multicenter, randomized, double-blind, phase IV trial (NCT01636947) enrolled adult South Korean patients with a broad range of tumor types who were scheduled to receive a single dose of ≥1 MEC agent. Patients were randomized to a 3-day regimen of aprepitant (aprepitant regimen) or placebo (control regimen) on top of ondansetron plus dexamethasone. The primary and key secondary efficacy endpoints were the proportions of subjects who achieved no vomiting and complete response (CR) during the overall phase.Results: Of the 494 randomized subjects, 480 were included in the modified intent-to-treat population. Response rates for no vomiting and CR in the overall phase were numerically higher for the aprepitant regimen compared with the control regimen groups, but failed to reach statistical significance (no vomiting 77.2 vs 72.0%; p = 0.191; CR 73.4 vs 70.4%; p = 0.458). Both the aprepitant and control regimens were generally well tolerated.Conclusion: A 3-day aprepitant regimen was numerically better but not statistically superior to a control regimen with respect to the achievement of no vomiting or CR during the overall phase in a non-AC MEC Korean population based on government reimbursement guidelines.Trial Registration: ClinicalTrials.gov NCT01636947 ( https://clinicaltrials.Gov/ct2/show/NCT01636947 ). [ABSTRACT FROM AUTHOR]

Purpose: Neo-ALL-IN (NCT 01275859) is a single-center, phase II study aimed to evaluate the efficacy and safety profiles of neoadjuvant letrozole plus lapatinib, as well as potential biomarkers, in postmenopausal women with ER- and HER2-positive (ER+HER2+) breast cancer.Methods: Postmenopausal ER+HER2+ breast cancer of stages II-III was eligible. Daily 2.5 mg letrozole plus 1500 mg lapatinib were administered for 18-21 weeks before surgery. Clinical responses were assessed by palpation with caliper, breast ultrasonography, mammogram, and/or MRI. Biologic samples were collected for biomarker analyses at three time points (baseline, day 14, and before surgery). Baseline fluorine-18 fluorodeoxyglucose and fluorine-18 fluoroestradiol PET-CT scans were performed.Results: Among 24 patients enrolled, 17 (70.8 %) completed planned neoadjuvant treatment, whereas 7 prematurely terminated the treatment and proceeded to surgery because of toxicity or progression; 2 patients showed definite progression, and 2 showed clinical regrowth by palpation regardless of minimal response. All patients eventually underwent breast cancer surgery. Toxicities were generally mild mostly within grades 1-2 except prolonged or recurrent grade 3 liver toxicities in 3 patients (13.6 %) regardless of sequential dose reduction, which finally led to discontinuation of treatment. The overall clinical response rates were 62.5 % (n = 15) including 1 CR in breast. However, no pathologic CR (ypT0-is N0) was achieved. SUVmax lower than 5.5 in baseline FES PET-CT (p = 0.007), baseline TILs over 20 % (p = 0.026), and decreased IHC ER Allred score after neoadjuvant treatment (p = 0.021) were significantly associated with adverse clinical response.Conclusions: When this chemo-free, combination neoadjuvant therapy with letrozole and lapatinib is given for Asian postmenopausal ER+HER2+ breast cancer, TILs, change of ER expression following neoadjuvant treatment, and SUVmax in baseline FES-PET are to be considered potential biomarkers in these patients. [ABSTRACT FROM AUTHOR]

Purpose: Antibiotics are widely used in the treatment of uncomplicated left-sided colonic diverticulitis. In Asian countries, however, right-sided colonic diverticulitis is more common than left-sided colonic diverticulitis. The aim of the present study was to evaluate the need for antibiotics in the treatment of uncomplicated right-sided colonic diverticulitis in an Asian population. Methods: Patients were randomized to two management strategies: antibiotics and no antibiotics. At 4–6 weeks after discharge, the patients in both groups underwent computed tomography or were contacted by phone to confirm the effectiveness of the treatment. The primary end point was the treatment failure rate of the initial treatment, and secondary end points were the length of hospital stay and total admission costs. Results: Patients were randomized to treatment with (61 patients) or without (64 patients) antibiotics. The rates of treatment failure in the antibiotics and no antibiotics groups were 1.7% and 4.6%, respectively, with no significant difference (P = 0.619). There was also no significant difference in the length of hospital stay between the groups (P = 0.983). Total admission costs were lower in the no antibiotics group than in the antibiotics group (US$1004.70 vs US$1112.40, respectively, P = 0.037). Conclusion: Conservative management of uncomplicated right-sided colonic diverticulitis without antibiotics shows similar treatment failure rates and length of hospital stay, and is associated with lower hospital costs, compared with standard antibiotic treatment. Therefore, conservative management can be considered as a safe treatment option. Trial registration: ClinicalTrial.gov No. NCT02314013 [ABSTRACT FROM AUTHOR]

Objectives: MALDI-TOF MS has been successfully used for empirical antibiotic selection. However, limited data are available regarding the usefulness of MALDI-TOF MS in common resistant organisms compared with rapid antimicrobial susceptibility testing (AST). We prospectively evaluated the usefulness of rapid AST, compared with MALDI-TOF MS, for optimal antibiotic selection by infectious disease (ID) physicians in patients with bacteraemia including polymicrobial infection.Methods: Three hundred and fifty-nine patients with positive blood culture were included for analysis. ID physicians prospectively decided on antibiotic regimens with consensus at each timepoint of receiving results of Gram stain, MALDI-TOF MS and rapid AST, the last of which was performed using QMAC-dRAST.Results: ID physicians with MALDI-TOF MS results chose optimal targeted antibiotics in 255 (71.0%) cases, with appropriate antibiotic selection in 303 (84.4%) cases. The proportion of optimal targeted antibiotic selection and appropriate antibiotic selection was significantly lower for resistant strains than for susceptible strains [62.5% versus 79.2% (P < 0.001) and 68.2% versus 100% (P < 0.001), respectively]. QMAC-dRAST results led to optimal antibiotic treatment in 95 (91.3%) of the 104 cases receiving non-optimal targeted antibiotics. Optimal targeted treatments based on QMAC-dRAST results were possible in 322 (98.2%) of the 328 cases with monobacterial infection and in 345 (96.1%) of the 359 cases with monobacterial and polymicrobial infection.Conclusions: MALDI-TOF MS has a high chance of failure in guiding ID physicians to optimal antibiotics, especially against resistant organisms. With increasingly common resistant organisms, rapid AST is needed to identify optimal targeted antibiotics early in bacteraemia. [ABSTRACT FROM AUTHOR]

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma for which standard treatment has yet to be established. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a suitable consolidation strategy for patients who respond to induction chemotherapy. The purpose of this study was to compare the outcome and toxicity profile of the combination of busulfan, cyclophosphamide, and etoposide (BuCyE) with that of the combination of thiotepa, busulfan, and cyclophosphamide (TBC) as conditioning regimens of upfront ASCT for consolidation therapy in PCNSL. The PCNSL registry data set, prospectively collected from March 1993 to May 2017 at Asan Medical Center, was reviewed retrospectively. Patients with objective response to induction chemotherapy who received BuCyE or TBC as conditioning regimen for ASCT were included in the analysis. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Among 241 patients with a diagnosis of PCNSL, 53 received ASCT as upfront consolidation therapy with TBC (28 patients) or BuCyE (25 patients) as conditioning regimen. No median OS or PFS was reached in the TBC group, while the BuCyE group reached a median OS of 4.9 years (p = 0.02) and median PFS of 1.1 years (p = 0.007). The incidence of oral mucositis, nausea, and vomiting was higher with TBC than BuCyE. The median admission duration and days to engraftment were similar between the two groups. Despite the greater incidence of adverse events, TBC showed better outcomes than BuCyE in terms of survival. [ABSTRACT FROM AUTHOR]

Primary intracranial squamous cell carcinoma (SCC) is a rare neoplasm associated with malignant transformation of benign epidermoid or dermoid cysts. The optimal treatment and prognosis of this rare disease are unclear. A comprehensive literature review identified all reports relevant to clinical presentation, treatment, and outcome of primary intracranial SCC. All available data were extracted from the included literature. Two patients diagnosed with malignant transformation of an epidermoid cyst in our institute were also included in the study. Survival analysis was conducted to determine the factors affecting patient outcomes. A total of 62 cases were identified and selected for the present study. The median survival regardless of treatment was 12.8 months. Median survival for patients treated with surgery alone and surgery with radiotherapy was 5 months and 35 months, respectively (P = 0.037). Patients who underwent gross total resection showed relatively increased survival compared with those who underwent subtotal resection (median, 48 months vs. 25 months; P = 0.067). Patients with leptomeningeal carcinomatosis had a significantly decreased median survival of 10 months, as opposed to 41 months (P = 0.005). Primary intracranial SCC shows poor prognosis, with controversial management. The results of this study indicate that complete resection of tumor when possible, followed by radiotherapy, is the optimal treatment for improving patient outcome. [ABSTRACT FROM AUTHOR]

Objectives: To compare the diffusion parameters of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) between the "reflux" and the "non-reflux" kidneys, and to evaluate the feasibility of using IVIM DWI to predict vesicoureteral reflux (VUR) in children with a urinary tract infection (UTI).Methods: Eighty-three kidneys from 57 pediatric patients with a UTI were classified into "reflux" and "non-reflux" groups according to voiding cystourethrography (VCUG) results. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (PF) were measured and compared in the renal pelvis of both groups. Four indices (D*/ADC, PF/ADC, D*/D, and PF/D) were calculated and receiver operating characteristic (ROC) curve analyses were performed.Results: VURs were detected on VCUG in 21 kidneys. PF and D* were significantly higher in the "reflux" group than in the "non-reflux" group. The indices were all significantly higher. The PF/D index showed the best diagnostic performance in predicting VUR in children with UTI (Az = 0.864).Conclusion: PF and D* were significantly higher in the "reflux" kidney than in the "non-reflux" kidney. Our new index (PF/D) could prove useful for predicting VUR.Key Points: • IVIM DWI is both radiation-free and contrast media-free. • IVIM DWI index is easily calculated by combining diffusion parameters. • IVIM DWI may help predict VUR in children with UTI. • PF is significantly higher in the "reflux" than the "non-reflux" kidneys. • A new VUR index, PF/D could prove useful for predicting VUR. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy of continuous epidural infusion analgesia (ED) with 0.2 % Ropivacaine versus IV PCA (Fentanyl) in spinal fusion surgery patients.Method: A prospective randomized comparative clinical trial. Patients were randomized into one of two groups-the epidural group (ED-51 patients) and the IV PCA group (IV-43 patients). The epidural catheter tip was placed one level cephalad to the level of the PLIF in patients in the ED group. Patients were assessed by determining the pain score, cumulative opioid requirement, adverse effects, and satisfaction.Results: Pain score comparisons between the ED group and the IV group, respectively, were as follows: immediate postoperative status: 2.1 ± 1.5 vs. 7.2 ± 2.1, p = 0.01; postoperative day 1: 2.3 ± 1.9 vs. 6.8 ± 2.3, p = 0.02; postoperative day 2: 1.9 ± 1.8 vs. 5.4 ± 2.1, p = 0.02; postoperative day 3: 1.5 ± 1.6 vs. 3.9 ± 1.9, p = 0.03; postoperative day 4: 3.8 ± 2.1 vs. 3.1 ± 1.9, p = 0.4. Lower levels of opioids were required in the ED group, and fewer opioid-related complications developed in the patients in this group. Complications related to the use of epidural catheters were comparable between the two groups. Patient satisfaction with postoperative pain control was higher in the ED group.Conclusion: In comparison with the use of IV PCA only, continuous epidural infusion of Ropivacaine resulted in lower pain scores and opioid consumption and higher patient satisfaction levels after posterior lumbar interbody fusion. [ABSTRACT FROM AUTHOR]

Objective We aimed to compare the efficacy, safety, and tolerability of a modified Atkins diet ( MAD) with the classic ketogenic diet ( KD) for the treatment of intractable childhood epilepsy. Methods From March 2011 to March 2014, 104 patients aged 1-18 years who had refractory epilepsy were randomly assigned to each diet group (, number NCT2100501). A seizure diary record was used to compare seizure frequencies with the baseline prediet seizure frequency at the third and sixth months after diet therapy initiation. Results Fifty-one patients were assigned to the KD and 53 patients to the MAD. The KD group had a lower mean percentage of baseline seizures compared with the MAD group at 3 months (38.6% for KD, 47.9% for MAD) and 6 months (33.8% for KD, 44.6% for MAD), but the differences were not statistically significant (95% confidence interval [ CI] 24.1-50.8, p = 0.291 for 3 months; 95% CI 17.8-46.1, p = 0.255 for 6 months). Instead, for patients aged 1-2 years, seizure outcomes were consistently much more favorable in patients consuming the KD compared with those consuming the MAD. The rate of seizure freedom at 3 months after diet therapy initiation was significantly higher (53% for KD, 20% for MAD, p = 0.047) in these patients. The MAD had advantages with respect to better tolerability and fewer serious side effects. Significance The MAD might be considered as the primary choice for the treatment of intractable epilepsy in children, but the classic KD is more suitable as the first line of diet therapy in patients <2 years of age. [ABSTRACT FROM AUTHOR]

Background Identification of the source of postpartum hemorrhage (PPH) is important for embolization because PPH frequently originates from non-uterine arteries. Purpose To evaluate the clinical importance of identifying the non-uterine arteries causing the PPH and the results of their selective embolization. Material and Methods This retrospective study enrolled 59 patients who underwent embolization for PPH from June 2009 to July 2016. Angiographic findings and medical records were reviewed to determine whether non-uterine arteries contributed to PPH. Arteries showing extravasation or hypertrophy accompanying uterine hypervascular staining were regarded as sources of the PPH. The results of their embolization were analyzed. Results Of 59 patients, 19 (32.2%) underwent embolization of non-uterine arteries. These arteries were ovarian (n = 7), vaginal (n = 5), round ligament (n = 5), inferior epigastric (n = 3), cervical (n = 2), internal pudendal (n = 2), vesical (n = 1), and rectal (n = 1) arteries. The embolic materials used included n-butyl cyanoacrylate (n = 9), gelatin sponge particles (n = 8), gelatin sponge particles with microcoils (n = 1), and polyvinyl alcohol particles (n = 1). In 13 patients, bilateral uterine arterial embolization was performed. Re-embolization was performed in two patients with persistent bleeding. Hemostasis was achieved in 17 (89.5%) patients. Two patients underwent immediate hysterectomy due to persistent bleeding. One patient experienced a major complication due to pelvic organ ischemia. One patient underwent delayed hysterectomy for uterine infarction four months later. Conclusion Non-uterine arteries are major sources of PPH. Detection and selective embolization are important for successful hemostasis. [ABSTRACT FROM AUTHOR]

Purpose: Self-expandable stents have enabled endovascular treatment of wide-necked aneurysms (ordinarily viewed as technically prohibitive), with favorable outcomes. However, the impact of stent type on occlusive stability has not been adequately investigated. In small-sized unruptured saccular aneurysms, we generated estimates of stent-assisted coil embolization outcomes during follow-up monitoring. Stent type and other risk factors linked to recanalization were analyzed.Methods: A cohort of 286 patients harboring 312 small-sized unruptured aneurysms (< 10 mm) was subjected to mid-term and extended follow-up monitoring after stent-assisted coiling. Three types of stents (Enterprise, 192; Neuroform, 27; LVIS, 93) were deployed in this population; all medical records and radiologic data of which were reviewed. Mid-term recanalization rates and related risk factors were assessed using binary logistic regression analysis.Results: A total of 49 aneurysms (15.7%) displayed recanalization at 6 months postembolization, with 34 and 15 instances of minor and major recanalization, respectively. Multivariate analysis indicated that wide-necked aneurysms (> 4 mm) (HR = 2.362; p = 0.017), incomplete occlusion at time of coiling (HR = 2.949; p = 0.002), and stent type (p = 0.048) were significant factors in mid-term recanalization, whereas hypertension (p = 0.095) and packing density ≤ 30% (p = 0.213) fell short of statistical significance. Compared with Enterprise (HR = 2.828) or Neuroform (HR = 4.206) stents, outcomes proved more favorable with use of LVIS.Conclusions: Above findings demonstrate that in addition to occlusive status at time of coil embolization and neck size, stent type may affect follow-up outcomes of stent-assisted coil embolization in small-sized aneurysms. LVIS (vs Enterprise or Neuroform stents) performed best during follow-up monitoring in terms of limiting recanalization. [ABSTRACT FROM AUTHOR]

Objective: To investigate sleep disturbances that induce cognitive changes over 4 years in nondemented elderlies.Methods: Data were acquired from a nationwide, population-based, prospective cohort of Korean elderlies (2,238 normal cognition [NC] and 655 mild cognitive impairment [MCI]). At baseline and 4-year follow-up assessments, sleep-related parameters (midsleep time, sleep duration, sleep latency, subjective sleep quality, sleep efficiency, and daytime dysfunction) and cognitive status were measured using the Pittsburgh Sleep Quality Index and Consortium to Establish a Registry for Alzheimer's Disease Assessment, respectively. We used logistic regression models adjusted for covariates including age, sex, education, apolipoprotein E genotype, Geriatric Depression Scale, Cumulative Illness Rating Scale, and physical activity.Results: In participants with NC, long sleep latency (>30 minutes), long sleep duration (≥7.95 hours), and late midsleep time (after 3:00 am) at baseline were related to the risk of cognitive decline at 4-year follow-up assessment; odds ratio (OR) was 1.40 for long sleep latency, 1.67 for long sleep duration, and 0.61 for late midsleep time. These relationships remained significant when these variables maintained their status throughout the follow-up period. Newly developed long sleep latency also doubled the risk of cognitive decline. In those with MCI, however, only long sleep latency reduced the chance of reversion to NC (OR = 0.69).Interpretation: As early markers of cognitive decline, long sleep latency can be used for elderlies with NC or MCI, whereas long sleep duration and relatively early sleep time might be used for cognitively normal elderlies only. Ann Neurol 2018;83:472-482. [ABSTRACT FROM AUTHOR]

Objectives We performed this study to investigate the association of prehospital supraglottic airway ( SGA) on neurologic outcome in cardiac arrest victims with adjustment of postresuscitation variables as well as prehospital and resuscitation variables. Methods This study was a retrospective study based on a multicenter prospective cohort registry from December 2013 to April 2016. According to the 28-day cerebral performance categories ( CPCs) scale, patients were divided into the good-outcome group ( CPC 1-2) and the poor-outcome group ( CPC 3-5). We compared the two groups with respect to demographic variables, prehospital and in-hospital resuscitation variables, and postresuscitation variables. Results A total of 869 cardiac arrest victims who received in-progress cardiopulmonary resuscitation ( CPR) were delivered to the emergency department of three hospitals, and 310 patients were admitted to the intensive care unit. The use of a prehospital SGA was independently associated with 28-day good neurologic outcome (odds ratio [ OR] = 7.88; 95% confidence interval [ CI] = 1.33-46.53; p = 0.023] when postresuscitation variables were adjusted, although there were no significant association with the acquisition of sustained return of spontaneous circulation ( OR = 0.992; 95% CI = 0.591-1.666; p = 0.976). Furthermore, a prehospital SGA was significantly associated with good neurologic outcome, especially in patients who received prolonged CPR (low flow time > 15 minutes; OR = 3.41; 95% CI = 1.23-9.45; p = 0.018) rather than in patients with nonprolonged CPR ( OR = 4.50; 95% CI = 0.75-27.13; p = 0.101). Conclusions When postresuscitation variables were adjusted, the prehospital SGA was independently associated with 28-day good neurologic outcome in cardiac arrest victims. [ABSTRACT FROM AUTHOR]

Purpose: Distinguishing non-neoplastic pituitary stalk lesions (non-NPSLs) from neoplastic pituitary stalk lesions (NPSLs) is a major concern in guiding treatment for a thickened pituitary stalk. Our study aimed to aid provide preoperative diagnostic assistance by combining clinical and magnetic resonance imaging (MRI) findings to distinguish non-NPSLs from NPSLs. Materials and methods: We recruited 158 patients with thickened pituitary stalk lesions visible on MRI. Laboratory findings included hypopituitarism, diabetes insipidus (DI), and hyperprolactinemia. MR images were assessed for anterior–posterior thickness (mm), diffuse pituitary stalk thickening, cystic changes, a high T1 signal, and glandular or extrasellar involvement. A diagnostic model was developed using a recursive partitioning logistic regression analysis. The model was validated in an independent dataset comprising 63 patients, and its diagnostic performance was compared with that of the original radiological reports. Results: A univariate analysis found significant associations of DI (P = 0.006), absence of extrasellar involvement (P = 0.002), and lower stalk thickness (P = 0.031) with non-NPSLs. A diagnostic model was created using the following parameters (in order of priority): 1) lack of extrasellar involvement, 2) stalk thickness < 5.3 mm, and 3) presence of DI. The diagnostic performance (area under the curve; AUC) of this model in the independent set was 0.813, representing a significant improvement over the original radiological reports (AUC: 0.713, P = 0.029). Conclusion: The joint diagnostic approach based on clinical and imaging-based factors robustly distinguished non-NPSLs from NPSLs. This approach could guide treatment strategies and prevent unnecessary surgery in patients with non-NPSL. [ABSTRACT FROM AUTHOR]

Background Some vascular malformations are difficult to manage with surgical treatment. Thus, percutaneous sclerotherapy has been utilized with several advantages over surgical treatment. Bleomycin is one of several sclerosing agents used for the treatment of vascular malformations. Objectives To evaluate therapeutic efficacy and safety of percutaneous sclerotherapy using bleomycin for the treatment of vascular malformations. Methods Thirty patients diagnosed with vascular malformations, including four with capillary malformations with nodular change, nine with lymphatic malformations, and 17 with venous malformations, were involved in the study. Patients received magnetic resonance imaging and pulmonary surveillance prior to the treatment. Clinical assessments for the degree of vascularity disappearance and adverse effects were performed by the investigator. Results Percutaneous sclerotherapy using bleomycin was performed in 3.2 sessions (mean) over 3 months (mean). Significant improvement was observed in 90.0% of all lesions. All lesions of capillary malformation with nodular change and lymphatic malformation demonstrated significant improvement, and 82.4% of lesions of venous malformation improved significantly. Seven patients (23.3%) complained of side effects including pain and headache. All occurred within 24 hours and were tolerable. Conclusions Percutaneous sclerotherapy using bleomycin is effective and tolerable in the treatment of vascular malformation through a percutaneous approach. Therefore, it could be applied usefully for vascular malformations by dermatologists. [ABSTRACT FROM AUTHOR]

Background:The limited efficacy of topical tacrolimus may result from insufficient frequency of application or amount applied in eczema patients. Objective:To investigate the frequency of application and amount of use of topical tacrolimus in patients with various types of eczema. Methods:The frequency of application and the applied amount of topical tacrolimus were assessed over two weeks. Results:A total of 200 eczema patients completed this study. The average number of applications per day was 1.75 ± 0.53, despite instructions to apply the topical tacrolimus twice daily. With respect to the frequency of application, 147 (73.5%) and 122 (61.0%) of patients followed the prescription in the first and second weeks, respectively. The average amount applied per 2% of total body surface area (TBSA) was 0.54 ± 0.52 g. Only 53 (26.5%) patients applied between 80 and 120% of expected amount of topical tacrolimus. Limitations:The frequency of application was self-reported, possibly resulting in limited accuracy. Conclusion:Korean patients with eczema tend to apply topical tacrolimus less frequently and in inappropriate amounts. Clear instructions regarding both the frequency and amount of application are needed to improve the therapeutic outcome with treatment with topical tacrolimus. [ABSTRACT FROM PUBLISHER]

Background: While pure mesenchymal stem cell (MSC) treatment for spinal cord injury (SCI) is known to be safe, its efficacy is insufficient. Therefore, gene-modified stem cells are being developed to enhance the effect of pure MSCs. We investigated the effect of stem cell therapy through the transfection of a Wnt3a-producing gene that stimulates axonal regeneration. Method: MSCs obtained from the human umbilical cord blood (hMSCs) were multiplied, cultivated, and transfected with the pLenti-Wnt3a-GFP viral vector to produce Wnt3a-secreting hMSCs. A total of 50 rats were injured with an Infinite Horizon impactor at the level of the T7-8 vertebrae. Rats were divided into five groups according to the transplanted material: (1) phosphate-buffered saline injection group (sham group, n = 10); (Pertz et al. Proc Natl Acad Sci USA 105:1931-1936, 39) Wnt3a protein injection group (Wnt3a protein group, n = 10); (3) hMSC transplantation group (MSC group, n = 10); (4) hMSCs transfected with the pLenti vector transplantation group (pLenti-MSC group, n = 10); (5) hMSCs transfected with the pLenti+Wnt3a vector transplantation group (Wnt3a-MSC group, n = 10). Behavioral tests were performed daily for the first 3 days after injury and then weekly for 8 weeks. The injured spinal cords were extracted, and axonal regeneration markers including choline acetyltransferase (ChAT), growth-associated protein 43 (GAP43), and microtubule-associated protein 2 (MAP2) were investigated by immunofluorescence, RT-PCR, and western blotting. Results: Seven weeks after the transplantation (8 weeks after SCI), rats in the Wnt3a-MSC group achieved significantly higher average scores in the motor behavior tests than those in the other groups ( p < 0.05). Immunofluorescent stains showed greater immunoreactivity of ChAT, GAP43, and MAP2 in the Wnt3a-MSC group than in the other groups. RT-PCR and western blots revealed greater expression of these proteins in the Wnt3a-MSC group than in the other groups ( p < 0.05). Conclusions: Wnt3a-secreting hMSC transplantation considerably improved neurological recovery and axonal regeneration in a rat SCI model. [ABSTRACT FROM AUTHOR]

Purpose: To compare the response to transcatheter arterial chemoembolization (TACE) between hepatocellular carcinoma (HCC) with paradoxical uptake on the hepatobiliary phase (HBP) (HCCpara) and HCC with defect on the HBP (HCCdef), and to identify some imaging features that can differentiate between two groups.Materials and Methods: Ninety-three HCCs from 54 patients who underwent gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) prior to TACE were included. HCCs were classified into two groups according to the signal intensity (SI) on the HBP: HCCpara and HCCdef. Using post-TACE computed tomography (CT) as a reference standard, initial compact lipiodol uptake was assessed and compared between groups. The arterial enhancement ratio (AER), SI ratios of the arterial phase and HBP, and presence of the capsule appearance were compared between groups. After initial response, local tumor recurrence within 6 and 18 months was evaluated based on follow-up CT or MRI.Results: Fifteen HCCpara and 78 HCCdef were included. Compared to HCCdef, HCCpara showed more frequent initial compact lipiodol uptake (p=0.009), larger mean size (p=0.019), lower AER (p=0.005), higher SI ratio of the HBP (p<0.0001), and more frequent capsule appearance (p<0.0001). Local tumor recurrence rate within 6 months was also significantly lower in HCCpara than in HCCdef (p=0.008).Conclusion: Despite larger size and lower AER, HCCpara showed more frequent initial compact lipiodol uptake and lower early local recurrence rate after TACE than did HCCdef. [ABSTRACT FROM AUTHOR]

Aim Hydronephrosis is a rare complication of systemic lupus erythematosus ( SLE). Bladder and/or gastrointestinal involvement in SLE are associated with development of hydronephrosis, but the management and treatment outcomes of hydronephrosis are largely unknown. Therefore, we investigated the clinical manifestations and factors associated with the treatment response in patients with SLE complicated by hydronephrosis. Method A retrospective analysis was performed of all 634 SLE patients who underwent computed tomography and/or ultrasonography between January 1998 and December 2013. We reviewed the clinical characteristics and treatment outcomes of patients with SLE-associated hydronephrosis. Results Hydronephrosis was identified in 15 patients with SLE complicated by cystitis and/or enteritis. All patients were treated initially with moderate to high doses of corticosteroids. A follow-up imaging study showed that 11 (73.3%) of 15 patients experienced improvements in hydronephrosis, and urinary obstruction was resolved without urological intervention in the majority of these patients (8/11, 72.7%). The four patients who experienced no improvement in hydronephrosis were older than those who responded to treatment (median age [interquartile range]; 43.0 [37.5-53.0] years vs. 28.0 [21.0-38.5] years; P = 0.026). In addition, delayed treatment (≥ 1 month after onset of symptoms) with corticosteroids was more frequently observed in the non-responding patients than in the responding patients ( P = 0.011). Conclusion Our findings suggest that treatment with corticosteroids alone leads to favorable outcomes in patients with SLE-associated hydronephrosis, except when treatment is delayed, particularly in elderly patients. [ABSTRACT FROM AUTHOR]

Background and purpose Transarterial access to dural arteriovenous fistulas (dAVFs) has been popularized by device improvements and novel embolic materials. However, this approach is limited in the cavernous sinus (CS) because of related complications and low cure rates. Although a transvenous approach, via ipsilateral inferior petrosal sinus (IPS), may be more suitable for CS-dAVFs, microcatheter delivery is occasionally impeded by ipsilateral IPS occlusion. Described herein is a microguidewire looping method to breach such occlusions, thus enabling access to CS lesions. Methods A microcatheter is initially advanced into the IPS orifice, and a microguidewire is passed into the occluded IPS. Looping is easily achieved through the resistance met. With greater support of the guiding catheter, the microguidewire (still looped) is then advanced into the CS. When nearing the CS, the microcatheter is further reinforced, and it is navigated along the microguidewire into the CS. Results This technique was applied in 10 instances of CS-dAVF with ipsilateral IPS occlusion, enabling ipsilateral access to the CS. In eight cases (80%), microdevice advancement was successful, culminating in effective transvenous coil embolization. Clinical and radiologic outcomes in all patients were excellent, with no delayed post-procedural cranial palsies. Conclusion This microguidewire looping technique enables safe and effective entry into the CS during transvenous coil embolization of CS-dAVFs with ipsilateral IPS occlusion. [ABSTRACT FROM AUTHOR]

Saturated fatty acids can activate Toll-like receptor 2 (TLR2) and TLR4 but polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA) inhibit the activation. Lipopolysaccharides (LPS) and lipopetides, ligands for TLR4 and TLR2, respectively, are acylated by saturated fatty acids. Removal of these fatty acids results in loss of their ligand activity suggesting that the saturated fatty acyl moieties are required for the receptor activation. X-ray crystallographic studies revealed that these saturated fatty acyl groups of the ligands directly occupy hydrophobic lipid binding domains of the receptors (or co-receptor) and induce the dimerization which is prerequisite for the receptor activation. Saturated fatty acids also induce the dimerization and translocation of TLR4 and TLR2 into lipid rafts in plasma membrane and this process is inhibited by DHA. Whether saturated fatty acids induce the dimerization of the receptors by interacting with these lipid binding domains is not known. Many experimental results suggest that saturated fatty acids promote the formation of lipid rafts and recruitment of TLRs into lipid rafts leading to ligand independent dimerization of the receptors. Such a mode of ligand independent receptor activation defies the conventional concept of ligand induced receptor activation; however, this may enable diverse non-microbial molecules with endogenous and dietary origins to modulate TLR-mediated immune responses. Emerging experimental evidence reveals that TLRs play a key role in bridging diet-induced endocrine and metabolic changes to immune responses. [ABSTRACT FROM AUTHOR]

Purpose: Mantle cell lymphoma (MCL) is a disease that frequently relapses and primarily affects elderly people. We performed an open-label, multi-center, phase II study to investigate the effect and quality of life (QoL) of treatment with vorinostat in combination with fludarabine, mitoxantrone and dexamethasone (V-FND) for relapsed or refractory MCL.Methods: The treatment schedule was composed of four cycles of induction treatment with V-FND and subsequent consolidation therapy involving autologous hematopoietic stem cell transplantation or six cycles of vorinostat maintenance. QoL was assessed using EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) every 2 cycles.Results: Data from a total of 20 patients were collected for an interim analysis. The median age was 67 years (range 49-75), and 14 or the patients (70 %) were male. The full course of V-FND induction treatment was completed in 11 patients, but only three completed all six cycles of maintenance therapy. Response to V-FND was not available in two patients. Among the other 18 patients, the objective response rate was 77.8 % (complete response in five patients + partial response in nine patients). Median progression-free survival was 9.3 months [95 % confidence interval (CI) 4.0-12.3]. Fifteen patients (75 %) experienced grade 3/4 toxicities. Analysis of QoL demonstrated significant deterioration of social functioning (p = 0.01), and significant aggravation of fatigue and nausea/vomiting (p = 0.04 and 0.01, respectively) after two cycles of V-FND induction.Conclusions: V-FND is effective in patients with relapsed or refractory MCL. However, significant toxicities were hurdles to sustained V-FND therapy. [ABSTRACT FROM AUTHOR]

Implantable devices have provided various potential diagnostic options and therapeutic methods in diverse medical fields. A variety of hard-material-based implantable electrodes have been developed. However, several limitations for their chronic implantation remain, including mechanical mismatches at the interface between the electrode and the soft tissue, and biocompatibility. Soft-material-based implantable devices are suitable candidates for complementing the limitations of hard electrodes. Advances in microtechnology and materials science have largely solved many challenges, such as optimization of shape, minimization of infection, enhancement of biocompatibility and integration with components for diverse functions. Significant strides have also been made in mechanical matching of electrodes to soft tissue. In this review, we provide an overview of recent advances in soft-material-based implantable electrodes for medical applications, categorized according to their implantation site and material composition. We then review specific applications in three categories: neuroprosthetics, neural signal recording, and neuromodulation. Finally, we describe various strategies for the future development and application of implantable, soft-material-based devices. [ABSTRACT FROM AUTHOR]

Study Objective: To assess the utility of TachoSil for achieving hemostasis after loop electrosurgical excision procedure (LEEP).Design: Case-control study (Canadian Task Force Classification II-2).Setting: University hospital.Patients: One hundred seventy-three patients who underwent LEEP.Interventions: Patients were managed by LEEP with application of TachoSil (TachoSil group, n=75) or without application of TachoSil (control group, n=94).Measurements and Main Results: Patient characteristics (age, specimen depth, resection margin, LEEP histopathology, or use of TachoSil) except for parity were similar between the two study groups. Severe bleeding requiring any intervention developed in 14% of patients (24 of 169 patients), without any statistically significant difference between the two groups (11% in the TachoSil group vs. 17% in the control group; P=0.274). On the logistic regression analysis, other potential clinico-pathologic parameters, including age, parity, specimen depth, involvement of the resection margin, and LEEP histopathology, were not correlated with severe bleeding after LEEP.Conclusion: The use of TachoSil may not reduce the incidence of severe bleeding after LEEP. [ABSTRACT FROM AUTHOR]

Background: In this study, we compared the dosimetric properties between Gamma Knife (GK) and Cyberknife (CK), and investigated the clinical implications in treating brain metastases (BMs). Methods: Between 2011 and 2013, 77 patients treated with either single-fraction GK for small BMs ( n = 40) or fractionated CK for large BMs >3 cm ( n = 37) were analyzed. Among a total of 160 lesions, 81 were treated with GK (median, 22 Gy) and 38 (large lesions) with three- or five-fraction CK (median, 35 Gy). The median tumor volume was 1.0 cc (IQR, 0.12-4.4 cc) for GK and 17.6 cc (IQR, 12.8-23.7 cc) for fractionated CK. A lesion-to-lesion dosimetric comparison was performed using the identical contour set in both systems. Results: The mean dose to tumor was significantly higher in GK by 1.25-fold ( P < 0.001), whereas normal tissue volume receiving 90-10 % of prescription dose was significantly larger in CK by 1.26-fold ( P < 0.001). Nevertheless, no differences were observed in local tumor control (rates at 1 year, 89.7 % vs 87.0 %; P = 0.594) and overall survival (median, 14 vs 16 months; P = 0.493) between GK and fractionated CK groups. The incidences of radiation necrosis were also not different (12.3 % vs 15.8 %; P = 0.443). Conclusions: Despite slightly inferior dosimetric properties of CK, fractionated CK for large BMs appears to be as effective and safe as single-fraction GK for small BMs, representing fractionation as an effective strategy for enhancing efficacy and moderating toxicity in stereotactic radiosurgery for BMs. [ABSTRACT FROM AUTHOR]

Sesamolin and sesamin are representative lignans found in sesame seed. The present study was designed to demonstrate the anti-cancer activity of sesamolin achieved by increasing the expression level of NKG2D ligands on Raji cells, which are derived from Burkitt's lymphoma. The anti-cancer activity of sesamolin was also compared with that of sesamin. The cytolysis activity of NK cells against Raji was elevated by the pretreatment of sesamolin on Raji, but not by sesamin. We found that higher NKG2D ligand expression increased the sensitivity of sesamolin-treated Raji to NK cell lysis, resulting from a more active ERK signaling pathway. Our results provide evidence that targeting the ERK signaling pathway may enhance the antitumor activity of lignans and that there is a potential immunotherapeutic value for cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the comparison of effectiveness between stellate ganglion block (SGB) and complex decongestive physiotherapy (CDT) in breast cancer-related lymphedema (BCRL) patients. Methods: The study is a retrospective matched cohort study. A total of 60 subjects who had secondary lymphedema after breast cancer treatments were included in this study. Thirty subjects who had SGB were matched with other 30 subjects treated with CDT, which is the standard therapy for BCRL. The groups were matched for age, duration of lymphedema, type of surgery, and history of lymph node dissection. SGB subjects received SGB three times, once every 2 weeks and CDT subjects were treated for 2 weeks. The circumferences of the forearm and upper arm were used as the outcome variable. These parameters were measured with baseline value before each treatment and repeated the evaluation after the treatments. We investigated the difference of circumferences within each treatment and compared the clinical effect between treatments. Results: Sixty subjects (mean age 58.2 ± 8.7) were treated with CDT and SGB each. There was no significant difference in demographic data including cancer treatment. The mean circumferences of the forearm and upper arm after CDT significantly reduced; forearm from 24.91 to 23.87 cm and upper arm from 30.52 to 29.58 cm ( p < 0.001). And the clinical effect of SGB was also significant; forearm from 24.90 to 23.64 cm and upper arm from 30.96 to 29.16 cm ( p < 0.001). The differences of the forearm between CDT and SGB was not significant, but the circumference of the upper arm was more reduced after SGB treatment (1.81 ± 1.21 cm) than CDT (0.94 cm ± 0.78 cm) ( p < 0.01). Conclusions: SGB is an effective treatment which can reduce the circumference of arm in breast cancer-related lymphedema patients and could be an alternative treatment for lymphedema. [ABSTRACT FROM AUTHOR]

Introduction: Although various protective techniques for treating wide-necked intracranial aneurysms currently exist and continue to evolve, their utility may be limited in some lesions with complex configurations, small-caliber channels, or inherently tortuous vascular patterns. Described herein is a modified coil protection technique as a novel adjunct for proper coil frame configuration. Methods: Initially, a microcatheter is passed into aneurysmal sac, and the first coil is inserted to build a frame. Inevitably, some coils may abut opposite poles of aneurysms and protrude into parent arteries. Should this happen, a second microcatheter may be placed at the site of coil protrusion, so that a separate and smaller coil may be partially deployed for protection. A framing coil may then be configured within aneurysmal sac, under protection of the secondary coil. Once the first coil is entirely in place, the remainder of second coil is carefully inserted, and additional coil may be inserted as needed via dual microcatheters. Results: This technique was successfully applied to 23 saccular intracranial aneurysms of internal carotid ( n = 8), middle cerebral ( n = 6), anterior cerebral ( n = 6), and superior cerebellar artery ( n = 3), combining stent protection in two patients and balloon remodeling in one. Selective endovascular treatment was effective as a result. Excellent outcomes were achieved in all patients, with no morbidity or mortality directly related to the modified procedure. Conclusion: As suggested by outcomes of this small study, our modified coil protection method may be a safe option if traditional coiling strategies are not feasible, enabling stable coil frame configuration in wide-necked aneurysms. [ABSTRACT FROM AUTHOR]

Background: The granisetron transdermal system (GTS) showed non-inferior efficacy to oral granisetron to control chemotherapy-induced nausea and vomiting (CINV) during multiday chemotherapy. We compared the efficacy and safety of GTS with that of intravenous and oral granisetron in Korean patients receiving moderately emetogenic chemotherapy (MEC). Patients and methods: A total of 276 patients were randomized into GTS ( n = 139, one patch on days 1-4) or control group ( n = 137, intravenous on day 1 and oral on days 2-4). The primary endpoint was the percentage of patients achieving complete response (CR) from chemotherapy initiation until 24 h after the final administration. Results: Out of 234 patients (112 in GTS and 122 in control group) included in the per protocol analysis, 97.9 % had gastrointestinal cancer and 76.9 % received 3-day chemotherapy. The GTS showed non-inferior efficacy achieving CR in 75.0 % of the patients; 74.6 % of the patients in the control group achieved CR (95 % confidence interval −10.73 to 11.55 %). The CR rate did not change after subgroup analyses by sex, age, and chemotherapy naivety and analysis per day and overall days of treatment. The GTS group showed sustained CR from day 1 to day 4. Patients' satisfaction, assessed using Functional Living Index-Emesis (FLI-E), showed no difference. Both treatments were well tolerated and safe. Conclusion: The GTS showed non-inferior efficacy to intravenous and oral granisetron. The safety, tolerability, and FLI-E scores of the GTS were comparable to those of control group. The GTS offers a convenient alternative option for relieving CINV in patients receiving MEC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ecabet sodium (ES) is a new nonsystemic anti-ulcer agent belonging to the category of gastroprotective agents. In this study we aimed to compare the efficacy of a combination therapy with lansoprazole (LS) followed by ES with LS alone in treating endoscopic submucosal dissection (ESD)-induced iatrogenic gastric ulcers. METHODS: Patients diagnosed with gastric adenomas or early gastric cancer were randomly divided into either the LS group (30 mg once daily for 4 weeks; n = 45) or the LS + ES group (LS 30 mg once daily for one week followed by ES 1500 mg twice daily for 3 weeks; n = 45). Four weeks after ESD, a followup endoscopy was conducted to evaluate the proportions of ulcer reduction and ulcer stages in the two groups. RESULTS: In all, 79 patients were included in the final analyses. Both treatment modalities were welltolerated in most patients, with a drug compliance of over 80%. There were no significant differences between the two groups in terms of the proportions of ulcer reduction (0.9503 ± 0.1215 in the LS group vs 0.9192 ± 0.0700 in the LS + ES group, P = 0.169) or ulcer stage (P = 0.446). The prevalence of adverse events related to drugs and bleeding were also similar between the two groups. CONCLUSION: Sequential therapy with LS + ES is as effective as LS alone against ESD-induced gastric ulcers. [ABSTRACT FROM AUTHOR]

Background: It has been well known that pediatric allergic rhinitis was associated with poor performance at school due to attention deficit. However, there were no cohort studies for the effect of treatment of allergic rhinitis on attention performance in pediatric population. Thus, the aim of this study was to investigate whether attention performance was improved after treatment in children with allergic rhinitis. Methods: In this ARCO-Kids (Allergic Rhinitis Cohort Study for Kids), consecutive pediatric patients with rhinitis symptoms underwent a skin prick test and computerized comprehensive attention test. According to the skin prick test results, the children were diagnosed as allergic rhinitis or non- allergic rhinitis. All of the patients were regularly followed up and treated with oral medication or intranasal corticosteroid sprays. The comprehensive attention tests consisted of sustained and divided attention tasks. Each of the tasks was assessed by the attention score which was calculated by the number of omission and commission errors. The comprehension attention test was repeated after 1 year. Results: A total of 797 children with allergic rhinitis and 239 children with non-allergic rhinitis were included. Initially, the attention scores of omission and commission errors on divided attention task were significantly lower in children with allergic rhinitis than in children with non-allergic rhinitis. After 1 year of treatment, children with allergic rhinitis showed improvement in attention: commission error of sustained (95.6±17.0 vs 97.0±16.6) and divided attention task (99.1±15.8 vs 91.8±23.5). Meanwhile, there was no significant difference of attention scores in children with non-allergic rhinitis. Conclusions: Our study showed that management of allergic rhinitis might be associated with improvement of attention. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the association between the efficacy of first-line cytotoxic chemotherapy plus bevacizumab and single-nucleotide polymorphisms (SNPs) of angiogenic genes in patients with advanced colorectal cancer (CRC). Methods: DNA was extracted from blood samples of 125 patients, and 12 SNPs were evaluated for association with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: The vascular endothelial growth factor A (VEGFA) rs833061 T/T was associated with superior ORR compared to its alternative genotypes (75.9 vs. 50.8%; p = 0.008), and the interleukin 8 rs4073 A/A genotype tended to be associated with poor ORR (45.0 vs. 66.0%; p = 0.067). The median PFS and OS were superior in patients with the fms-related tyrosine kinase 1 (FLT1) rs9513070 A/A genotype (8.7 vs. 6.6 months; p = 0.001 and 26.4 vs. 16.1 months; p = 0.038, respectively). The kinase insert domain receptor rs1531289 G/G genotype tended to be associated with improved PFS (8.0 vs. 7.1 months; p = 0.069). In haplotype analysis, the FLT1 rs9513070/rs9554320/rs9582036 GCA haplotype was associated with inferior PFS and OS (p = 0.004 and p = 0.041, respectively). Conclusion: The VEGFA rs833061 SNP is associated with the ORR, and the FLT1 rs9513070 SNP and FLT1 GCA haplotypes are associated with PFS and OS in advanced CRC patients treated with cytotoxic chemotherapy plus bevacizumab. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Various lasers have been used for the treatment of erythematotelangiectatic rosacea ( ETR) that does not respond to systemic or topical therapy. The pulsed dye lasers ( PDLs) are an effective option for ETR, and the purpuragenic fluence proved to be superior until now. Given that purpura and subsequent possible postinflammatory hyperpigmentation ( PIH) are occasionally unbearable in some patients, and several studies using the low nonpurpuragenic fluence were reported. To deliver the sufficient high fluence of a PDL without generating purpura, we designed the fractionation of high fluence using five passes and longer pulse duration (6 milliseconds) of a PDL in succession. A total of eight patients with ETR were enrolled in this study; all patients were treated with PDL 10 times at 2-week intervals. Erythema and telangiectasia scores, as well as improvement, were assessed by two physicians using the digital photographs. Moderate-to-marked improvement was achieved in most of the patients, and erythema and telangiectasia scores were significantly decreased. Purpura and PIH were not reported in all patients. The fractionation of high-fluence, long-pulsed 595 nm PDL is a very safe and effective treatment for ETR. [ABSTRACT FROM AUTHOR]

Introduction: Single-incision laparoscopic cholecystectomy (SILC) has been increasing in use steadily, and many researchers have reported the safety and feasibility of SILC. However, most studies were confined to selected patients and excluded patients with acute inflammation. In this study, we evaluated the safety and feasibility of SILC with our technique in patients with acute cholecystitis. Patients and Methods: Ninety-six patients with acute cholecystitis undergoing laparoscopic cholecystectomy at Uijeonbu St. Mary's Hospital (Uijeongbu, Korea) between October 2011 and December 2012 were retrospectively reviewed. SILC was performed in 49 patients, and conventional three-port laparoscopic cholecystectomy was performed in 47 patients. Patient demographics and operative outcomes were compared between groups to evaluate the safety and feasibility of SILC using our technique. Results: There were no differences between groups in demographics except for the sex ratio. SILC was more often performed in female patients (69% versus 34%, P=.001). There were no statistically significant differences between groups in terms of operation time, critical view of safety identification time, iatrogenic gallbladder perforation, port-site seroma, and postoperative hospital stay, respectively. One patient in each group required conversion to open cholecystectomy because of massive bleeding. Conclusions: This study showed that needlescopic grasper-assisted SILC with our technique is acceptable not only in selected patients but also in patients with acute cholecystitis. Lateral and cephalad retraction using a needlescopic grasper and a snake retractor can make SILC safe and easy in acute cholecystitis through better visualization of the triangle of Calot. [ABSTRACT FROM AUTHOR]

Introduction: Superior cerebellar artery (SCA) aneurysms have distinctive morphologic configurations and vascular origins. Herein, we have analyzed the angioarchitectural characteristics of SCA aneurysms and outcomes achieved through endovascular treatment. Methods: Data accruing prospectively from January, 2002 to September, 2013 yielded 53 SCA aneurysms in 53 patients. Each lesion was classified as either basilar artery (BA), BA-SCA, or SCA type, according to the nature of incorporated vasculature. Clinical and morphologic outcomes were assessed, with emphasis on technical aspects of treatment. Results: Angles formed by SCA and posterior cerebral artery were obtuse (124.8 ± 29.1°) on sides ipsilateral to aneurysms, differing significantly from contralateral counterparts (44.8 ± 22.0°) ( p < 0.001). The most common type of aneurysm was BA-SCA (54.7 %), followed by SCA (28.3 %) and BA (17.0 %), and BA type aneurysms were the largest in size. Steam-shaped S-configured microcatheters ( n = 19, 67.9 %) facilitated aneurysm selection for approach via contralateral vertebral artery ( n = 28), whereas pre-shaped 45/90/J microcatheters ( n = 21, 84.0 %) primarily were used for ipsilateral vertebral artery approach ( n = 25). Single-microcatheter technique (52.8 %) was most often applied, followed by double-microcatheter (34.0 %), stent-assisted (9.4 %), and microcatheter-protection techniques (3.8 %). Aneurysmal occlusion was satisfactorily achieved in 45 lesions (82.1 %), with no procedure-related morbidity and mortality. In follow-up monitoring of 46 patients for a mean period of 25.8 ± 24.4 months, only a single instance of major recanalization (2.2 %) occurred. Conclusion: Coil embolization of SCA aneurysms is a safe and effective treatment modality, enabling individualized procedural strategies to accommodate distinctive angio-anatomic configurations. [ABSTRACT FROM AUTHOR]

Background: There are various treatment modalities of onychomycosis. Of these, however, oral antifungal therapies are complicated by potential drug interactions and systemic effects, and the surgical treatment can result in prolonged pain. Therefore, a new, safe and effective therapy is needed that can improve the aesthetic appearance of the nails. Objective: The purpose of this study was to evaluate the effect of treatment of onychomycosis with a 1,064-nm long-pulsed Nd:YAG laser. Methods: 13 patients (31 toenails, 12 fingernails) received five treatment sessions at 4-week intervals with a 1,064-nm long-pulsed Nd:YAG laser. Parameters for each treatment were 6 mm spot size, 5 J/cm2 fluence, 0.3 ms pulse duration and 5 Hz pulse rate. Results: Of the 13 patients, 8 (61.5%) were women and 5 were men. The mean age of the patients was 62. Of the 43 nails, 4 (9.3%) achieved a complete cure (9.3%), 8 had excellent treatment outcomes (18.6%) and 31 had good treatment outcomes (72%). None of the 13 patients experienced any discomfort except for a mild burning sensation and there were no adverse effects. Conclusions: Our results demonstrate that the 1,064-nm long-pulsed Nd:YAG laser could be a safe and effective treatment modality in the management of patients with onychomycosis. [ABSTRACT FROM AUTHOR]

Introduction: Protective/remodeling techniques for treating wide-necked intracranial aneurysms are constantly sought. However, their utility may be limited in lesions that incorporate the orifice of acute-angled efferent branch vessels. Furthermore, passage of a protective microcatheter may be challenging if a small branch is extremely tortuous. This study was conducted to explore a novel method of treating wide-necked aneurysms, utilizing microguidewire protection. Methods: A microcatheter is first passed into parent artery (proximal to aneurysm) to position a microguidewire proximally in the involved branch. A second microcatheter is then inserted into aneurysmal sac. Advancement of the first microcatheter forces the microguidewire to shift, thus covering aneurysmal neck. A framing coil may then be placed within aneurysmal sac, under microguidewire protection. After completing initial coil insertion, easing of tension on the microcatheter allows separation of protective microguidewire and frame coil, confirming stability of the initial coil. Results: This technique was applied to 11 intracranial saccular aneurysms of M1 segment ( n = 6), middle cerebral artery bifurcation ( n = 4), and anterior communicating artery ( n = 1) with success, combining stent protection in two patients. Coil embolization was thus facilitated, resulting in excellent outcomes for all patients. No morbidity or mortality was directly related to microguidewire protection. Conclusion: Our small study suggests that microguidewire protection may be a safe alternative, if traditional remodeling or protective options are infeasible due to intrinsic vascular properties. This technique is particularly suited for treatment of wide-necked aneurysms where passage of protective microcatheters into involved branches is not achievable. [ABSTRACT FROM AUTHOR]

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Objective: Gemigliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor used in the treatment of type 2 diabetes mellitus. This study evaluated possible pharmacodynamic and pharmacokinetic interactions between gemigliptin and metformin and investigated their tolerability. Methods: A randomized, open-label, multiple-dose, three-treatment, three-period, three-sequence crossover study was conducted in healthy male subjects. Twenty-seven subjects received gemigliptin (50 mg once daily), metformin (1,000 mg twice a day), or both drugs for 7 days per dosing period. Blood samples were drawn over 24 h on the seventh day of each period for pharmacokinetic and pharmacodynamic evaluations, including plasma DPP-4 activity and total/active glucagon-like peptide-1 (GLP-1) levels. Meal tolerance tests were conducted for pharmacodynamic assessment on the eighth day. Safety and tolerability were evaluated using adverse events, vital signs, ECGs, and clinical laboratory tests. Results: Coadministration of gemigliptin and metformin had no significant effect on the pharmacokinetics of gemigliptin or metformin. The inhibition of DPP-4 by gemigliptin was not affected by coadministration with metformin. Co-therapy of gemigliptin and metformin showed additional effects by increasing plasma active GLP-1 concentrations and lowering serum glucose levels. The plasma glucagon level was lower in co-therapy than with metformin monotherapy. The coadministration of gemigliptin and metformin was well-tolerated without serious adverse events. Conclusions: Coadministration of gemigliptin and metformin showed beneficial anti-diabetic effects without pharmacokinetic drug-drug interactions. [ABSTRACT FROM AUTHOR]

Background: Although endoscopic submucosal dissection (ESD) is widely used to treat gastric neoplasms, there is no consensus for the optimal treatment for ESD-induced ulcers. We compared efficacy between 4 and 8 weeks of lansoprazole treatment for iatrogenic gastric ulcers that developed after ESD. Methods: Eighty-four patients who were diagnosed with gastric adenoma or early gastric cancer were enrolled and randomly assigned to treatment with lansoprazole (30 mg/day) for 4 or 8 weeks. Eight weeks after ESD, we conducted follow-up endoscopy to compare ulcer stage and ulcer reduction ratio (dividing the ulcer dimension at 8 weeks by the initial ulcer dimension) between the two groups. Results: From the 84 patients, 69 patients were included in the final analysis, with 34 in the 4-week group and 35 in the 8-week group. Eight weeks after ESD, there were no significant difference observed between the two groups in terms of the ulcer stage (68 % in the scar stage in the 4-week group vs. 69 % in the 8-week group, P = 0.93) or the ulcer reduction ratio (0.0081 ± 0.015 in the 4-week group vs. 0.0037 ± 0.008 in the 8-week group, P = 0.15). Also, in the subgroup analysis among the patients with large ulcers (>30 mm), those parameters were not different. Conclusions: For ESD-induced gastric ulcers, treatment with lansoprazole for 4 weeks was as effective as treatment for 8 weeks. Considering cost-effectiveness, proton pump inhibitor therapy for 4 weeks may be sufficient for ESD-induced gastric ulcers. [ABSTRACT FROM AUTHOR]

Although propofol has been reported to offer neuroprotection against cerebral ischemia injury, its impact on cerebral edema following ischemia is not clear. The objective of this investigation is to evaluate the effects of propofol post-treatment on blood-brain barrier (BBB) integrity and cerebral edema after transient cerebral ischemia and its mechanism of action, focusing on modulation of aquaporins (AQPs), matrix metalloproteinases (MMPs), and hypoxia inducible factor (HIF)-1α. Cerebral ischemia was induced in male Sprague-Dawley rats (n = 78) by occlusion of the right middle cerebral artery for 1 h. For post-treatment with propofol, 1 mg kg min of propofol was administered for 1 h from the start of reperfusion. Nineteen rats undergoing sham surgery were also included in the investigation. Edema and BBB integrity were assessed by quantification of cerebral water content and extravasation of Evans blue, respectively, following 24 h of reperfusion. In addition, the expression of AQP-1, AQP-4, MMP-2, and MMP-9 was determined 24 h after reperfusion and the expression of HIF-1α was determined 8 h after reperfusion. Propofol post-treatment significantly reduced cerebral edema ( P < 0.05) and BBB disruption ( P < 0.05) compared with the saline-treated control. The expression of AQP-1, AQP-4, MMP-2, and MMP-9 at 24 h and of HIF-1α at 8 h following ischemia/reperfusion was significantly suppressed in the propofol post-treatment group ( P < 0.05). Propofol post-treatment attenuated cerebral edema after transient cerebral ischemia, in association with reduced expression of AQP-1, AQP-4, MMP-2, and MMP-9. The decreased expression of AQPs and MMPs after propofol post-treatment might result from suppression of HIF-1α expression. [ABSTRACT FROM AUTHOR]

Objective. Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) is one of the active components present in the root and rhizome of Rheum palmatum. It has been shown to contain biological activity (antitumour, antibacterial, diuretic and vasorelaxant effects). However, the mechanisms underlying the anti-arthritic effect of emodin have not been elucidated. Here we investigated whether emodin treatment would modulate the severity of the disease in an experimental arthritis model.Methods. We evaluated the effects of emodin on CIA mice in vivo.Results. The pathological processes of RA are mediated by a number of cytokines and MMPs. Expression of these proinflammatory mediators is controlled by nuclear factor-κB (NF-κB). This study was performed to explore the effect of emodin on control of the NF-κB activation pathway and to investigate whether emodin has anti-inflammatory effects in CIA mice in vivo. Emodin inhibited the nuclear translocation and DNA binding of NF-κB subunits, which were correlated with its inhibitory effect on cytoplasmic IκBα degradation in CIA mice. These events further suppressed chemokine production and MMP expression. In addition, emodin inhibited the osteoclast differentiation induced by M-CSF and receptor activation of NF-κB ligand in bone marrow macrophages.Conclusion. These findings suggest that emodin exerts anti-inflammatory effects in CIA mice through inhibition of the NF-κB pathway and therefore may have therapeutic value for the treatment of RA. [ABSTRACT FROM AUTHOR]

Abstract: Laminaria japonica is a brown alga, which is consumed widely in Korea, Japan, and China. This study investigated the antimicrobial activity of ethanol extracts of L. japonica against oral microbial species to assess the possible application of L. japonica extracts in dental care products. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined in culture medium using a microdilution method. The MICs of ethanol extracts of L. japonica with oral streptococci were 62.5–500 μg/ml and the MBCs were 125–1000 μg/ml. The MICs of Actinomyces naeslundii and Actinomyces odontolyticus were 250 and 62.5 μg/ml, respectively. The MBCs of A. naeslundii and A. odontolyticus were 500 and 250 μg/ml, respectively. The MICs were 250 and 62.5 μg/ml for Fusobacterium nucleatum and Porphyromonas gingivalis, respectively. The killing of Streptococcus mutans and P. gingivalis was dependent on the incubation time. The killing of S. mutans, A. odontolyticus, and P. gingivalis was significantly dependent on the extract concentration. Bacterial treatment with L. japonica extracts changed the cell surface texture of S. mutans, A. odontolyticus, and P. gingivalis. The results of this study suggest that L. japonica extracts may be useful for the development of antimicrobial agents to combat oral pathogens. [Copyright &y& Elsevier]