Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability

To develop a hyaluronic microsphere with the improved oral bioavailability of poorly water-soluble cyclosporin A (CsA), the microspheres were prepared with varying ratios of sodium hyaluronate (HA)/sodium lauryl sulfate (SLS)/CsA using a spray-drying technique. The effects of HA and SLS on the dissolution and solubility of CsA in microspheres were investigated. The CsA-microsphere prepared with HA/SLS/CsA at the ratio of 4/2/1 gave the highest solubility and dissolution rate of CsA among those formulae tested. As solubility and dissolution rate of CsA were increased about 17- and 2-fold compared to CsA powder, respectively, this CsA-microsphere was selected as an optimal formula for oral delivery in rats. The CsA-microsphere and Sandimmun neoral sol gave significantly higher blood levels compared with CsA powder alone. Moreover, the AUC, T(max) and C(max) values of CsA in CsA-microsphere were not significantly different from those in Sandimmun neoral sol in rats, indicating that CsA-microsphere was bioequivalent to the commercial product in rats. Our results demonstrated that the CsA-microsphere prepared with HA and SLS, with improved bioavailability of CsA, might have been useful to deliver a poorly water-soluble CsA.     

Brief Report: Adenosine A2A receptor blockade prevents cisplatin-induced impairments in neurogenesis and cognitive function

Chemotherapy-induced cognitive impairment (CICI) has emerged as a significant medical problem without therapeutic options. Using the platinum-based chemotherapy cisplatin to model CICI, we revealed robust elevations in the adenosine A_2A receptor (A_2AR) and its downstream effectors, cAMP and CREB, by cisplatin in the adult mouse hippocampus, a critical brain structure for learning and memory. Notably, A_2AR inhibition by the Food and Drug Administration–approved A_2AR antagonist KW-6002 prevented cisplatin-induced impairments in neural progenitor proliferation and dendrite morphogenesis of adult-born neurons, while improving memory and anxiety-like behavior, without affecting tumor growth or cisplatin’s antitumor activity. Collectively, our study identifies A_2AR signaling as a key pathway that can be therapeutically targeted to prevent cisplatin-induced cognitive impairments.     

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).     

Association between metabolic syndrome and left ventricular geometric change including diastolic dysfunction

BackgroundWe investigated the association between individual components of metabolic syndrome (MetS) and left ventricular (LV) geometric changes, including diastolic dysfunction, in a large cohort of healthy individuals.MethodsOverall, 148 461 adults who underwent echocardiography during a health‐screening program were enrolled. Geographic characteristics on echocardiography and several markers of LV relaxation function were identified according to individual MetS components. Univariate linear regression analysis and a multivariate regression model adjusted for factors known to influence LV relaxation function were conducted.ResultsThe prevalence of LV diastolic dysfunction (LVDD) was higher in the MetS group than in the non‐MetS group (0.56% vs. 0.27%, p < .001). In univariate and multivariate analyses, E/A ratio, e′ velocity, and left atrial volume index were significantly associated with each component of MetS and covariates (all p ≤ .001). In the age‐ and sex‐adjusted model, MetS was significantly associated with LVDD (odds ratio [95% confidence interval], 1.350 [1.103, 1.652]). However, subjects with more MetS components did not have a significantly higher risk of LVDD. As the analysis was stratified by sex, the multivariate regression model showed that MetS was significantly associated with LVDD only in men (1.3 [1.00, 1.68]) with higher risk in more MetS component (p for trend < .001). In particular, triglyceride (TG) and waist circumference (WC) among MetS components were significantly associated with LVDD in men.ConclusionsMetS was associated with the risk of LVDD, especially in men, with a dose‐dependent association between an increasing number of components of MetS and LVDD. TG and WC were independent risk factors for LVDD in men.     

Comparison of the background echotexture between automated breast ultrasound and handheld breast ultrasound

This study aimed to compare the background echotexture (BE) between automated breast ultrasound (ABUS) and handheld breast ultrasound (HHUS) and evaluate the correlation of BE with mammographic (MG) density and background parenchymal enhancement (BPE) on magnetic resonance imaging (MRI). A total of 212 women with newly diagnosed breast cancer who had undergone preoperative ABUS, HHUS, MG, and MRI were included. Two breast radiologists blinded to the menopausal status analyzed the BE of the contralateral breasts of the patients with breast cancer in consensus. The MG density and BPE of breast MRI on the radiologic reports were compared with the BE in the ultrasound. We used the cumulative link mixed model to compare the BE and Spearman rank correlation to evaluate the association between BE with MG density and BPE. BE was more heterogeneous in ABUS than in HHUS (P < .001) and in the premenopausal group than in the postmenopausal group (P < .001). The heterogeneity of BE in the premenopausal group was higher with ABUS than with HHUS (P = .013). BE and MG density showed a moderate correlation in the postmenopausal group, but a weak correlation in the premenopausal group. BE and BPE showed moderate correlations only in the premenopausal group. ABUS showed a more heterogeneous BE, especially in the premenopausal group. Therefore, more attention is required to interpret ABUS screening in premenopausal women.     

Prevalence and risk of colorectal polyps among the Korean population under 50 years

Colorectal cancer is a common cancer; generally, adults aged ≥ 50 years are screened using stool occult blood tests and colonoscopy. However, colorectal adenoma and cancer have been found in patients under the aged of 50, and studies on characteristics and risk factors in young patients are lacking. We evaluated the prevalence and risk factors of colorectal adenoma and cancer in young adults aged under 50 years.We retrospectively analyzed 570 individuals aged under 50 years who underwent colonoscopy at the Haeundae Paik Hospital, Korea, from January to June 2018. Logistic regression model was used to identify the risk factors for colorectal adenoma and colorectal cancer.The prevalence of colorectal adenoma in group of 19–29 years was 3.2% (1 of 31), 30–39 years was 13.8% (30 of 217) and in the group of 40–49 years was 21.1% (68 of 322) (P = .009). In multivariable analysis, age over 45 years (adjusted odds ratio [OR], 1.941; 95% confidence interval [CI], 1.187–3.172; P = .008) and male sex (adjusted OR, 1.711; 95% CI, 1.044–2.806; P = .033) were independent risk factors for colorectal neoplasia including cancer.The prevalence of colorectal adenoma increases as the age increased in young adults under 50 years of age, especially after the age of 45 years, the risk of colorectal neoplasia increases; hence, early screening should be considered before the age of 50 years.     

Unusual chondroblastoma of the hand with large extraosseous soft tissue component

Chondroblastoma is a rare, benign primary cartilaginous bone tumor that typically arises in the epiphyses of the long bones. Radiologically, a well-defined lytic lesion with thin sclerotic margins is commonly found. The tumor is characterized histologically as an admixture of chondroblasts and multinucleated giant cells with chondroid matrix and pericellular calcifications. We present a case of a chondroblastoma of the hand with an unusual large extraosseous soft tissue component. The mass demonstrated diffuse calcifications and radiolucent lesions in the dorsal aspect of the hamate and metacarpals. Differential diagnoses included synovial chondromatosis, soft tissue chondroma, and tenosynovial giant cell tumor. The patient underwent open biopsy of the mass with plans for excision. Final histopathologic diagnosis was of chondroblastoma of the hamate with a large soft tissue component. A marginal excision of the lesion with curettage and cementation was performed.     

Comparison of the effects of inhalational and total intravenous anesthesia on quality of recovery in patients undergoing endoscopic transsphenoidal pituitary surgery: a randomized controlled trial

Background: Endoscopic transsphenoidal pituitary surgery has shown promising results. However, fast and high-quality recovery after this procedure remains a challenge for neuroanesthesiologists. This study aimed to compare the quality of recovery after transsphenoidal pituitary surgery between patients who received inhalational anesthesia with sevoflurane and patients who received propofol-based total intravenous anesthesia (TIVA).Methods: Eighty-two patients undergoing transsphenoidal pituitary surgery were randomized to receive either sevoflurane inhalation with manual infusion of remifentanil (sevoflurane group) or effect-site target-controlled infusion of propofol and remifentanil (TIVA group). The primary outcome was the 40-item Quality of Recovery (QoR-40) score on postoperative day 1. The QoR-40 questionnaire was completed by patients the day before surgery and on postoperative days 1 and 2. Emergence agitation and recovery characteristics were also assessed.Results: There were no significant differences between the groups in the global QoR-40 scores on both postoperative days 1 and 2 (difference -8.7, 95% CI -18.0 to 0.7, and P = 0.204; -3.6, 95% CI -13.0 to 5.8, and P > 0.999, respectively). The time to verbal response and time to extubation were significantly shorter in the sevoflurane group than in the TIVA group (P < 0.001 and P < 0.001, respectively). However, the incidence of emergence agitation was lower in the TIVA group than in the sevoflurane group (P < 0.001).Conclusions: Both inhalational anesthesia with sevoflurane and propofol-based TIVA were appropriate anesthetic techniques for patients undergoing endoscopic transsphenoidal pituitary surgery in terms of the quality of recovery up to 2 days postoperatively. Rapid emergence was observed in the sevoflurane group, while smooth emergence was observed in the TIVA group.     

Spleen stiffness-spleen size-to-platelet ratio risk score as noninvasive predictors of esophageal varices in patients with hepatitis B virus-related cirrhosis

This study was conducted to evaluate the predictive value of spleen stiffness-spleen size-to-platelet ratio risk score (SSPS) as a noninvasive predictor of esophageal varices (EVs) and to compare it with others.In this retrospective study, from April 2017 to October 2018, a total of 65 patients with hepatitis B virus-related cirrhosis who underwent the liver and spleen stiffness (LS, and SS) measurements by 2 dimensional-shear wave elastography and endoscopic evaluation for EVs were enrolled. Liver stiffness-spleen size-to-platelet ratio risk score (LSPS) and SSPS were calculated. The prognostic values were assessed by the area under the receiver operating characteristic curve (AUC).Twenty-six patients had no EV on endoscopy. Among 39 patients who had EVs, 12 patients had high risk EVs. The AUCs of the LS value, SS value, LSPS, and SSPS for predicting EVs were 0.72, 0.77, 0.80, and 0.85, respectively. The AUCs of the LS value, SS value, LSPS, and SSPS for predicting high-risk EVs were 0.55, 0.78, 0.67, and 0.80, respectively. SSPS had the highest specificity, at 96.15%, for predicting EVs.SSPS may be beneficial to exclude from having EVs and it is expected that the frequency of performing endoscopies for screening EVs can be reduced.     

Immunogenicity and Reactogenicity of Ad26.COV2.S in Korean Adults: A Prospective Cohort Study

BackgroundAs the coronavirus disease 2019 (COVID-19) pandemic continues, there are concerns regarding waning immunity and the emergence of viral variants. The immunogenicity of Ad26.COV2.S against wild-type (WT) and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated.MethodThis prospective cohort study was conducted between June 2021 and January 2022 at two university hospitals in South Korea. Healthy adults who were scheduled to be vaccinated with Ad26.COV2.S were enrolled in this study. The main outcomes included anti-spike (S) IgG antibody and neutralizing antibody responses, S-specific T-cell responses (interferon-γ enzyme-linked immunospot assay), solicited adverse events (AEs), and serious AEs.ResultsFifty participants aged ≥ 19 years were included in the study. Geometric mean titers (GMTs) of anti-S IgG were 0.4 U/mL at baseline, 5.2 ± 3.0 U/mL at 3–4 weeks, 55.7 ± 2.4 U/mL at 5–8 weeks, and 81.3 ± 2.5 U/mL at 10–12 weeks after vaccination. GMTs of 50% neutralizing dilution (ND50) against WT SARS-CoV-2 were 164.6 ± 4.6 at 3-4 weeks, 313.9 ± 3.6 at 5–8 weeks, and 124.4 ± 2.6 at 10–12 weeks after vaccination. As for the S-specific T-cell responses, the median number of spot-forming units/10⁶ peripheral blood mononuclear cell was 25.0 (5.0–29.2) at baseline, 60.0 (23.3–178.3) at 5-8 weeks, and 35.0 (13.3–71.7) at 10–12 weeks after vaccination. Compared to WT SARS-CoV-2, ND50 against Delta and Omicron variants was attenuated by 3.6-fold and 8.2-fold, respectively. The most frequent AE was injection site pain (82%), followed by myalgia (80%), fatigue (70%), and fever (50%). Most AEs were grade 1–2, and resolved within two days.ConclusionSingle-dose Ad26.COV2.S was safe and immunogenic. NAb titer and S-specific T-cell immunity peak at 5–8 weeks and rather decrease at 10–12 weeks after vaccination. Cross-reactive neutralizing activity against the Omicron variant was negligible.