Purpose: Placing dental implants in areas with low bone density or in conditions where bone healing is suppressed is challenging for clinicians. An experiment using a rodent model was performed with the aim of determining the efficacy of host modulation by increasing the systemic level of cholesterol sulfate (CS) using Irosustat in the context of the bone healing process around dental implants. Methods: In 16 ovariectomised female Sprague-Dawley rats, 2 implant fixtures were placed in the tibial bones (1 fixture on each side). At 1 week after surgery, the high-CS group (n=8) received Irosustat-mixed feed, while the control group (n=8) was fed conventionally. Block specimens were obtained at 5 weeks post-surgery for histologic analysis and the data were evaluated statistically (P<0.05). Results: Unlike the high-CS group, half of the specimens in the control group demonstrated severe bone resorption along with a periosteal reaction in the cortex. The mean percentages of bone-to-implant contact (21.5%) and bone density (28.1%) near the implant surface were significantly higher in the high-CS group than in the control group (P<0.05), as was the number of Haversian canals (by 5.3). Conclusions Host modulation by increasing the CS level may enhance the osseointegration of dental implants placed under conditions of impaired bone healing.

Background and Objectives: Heart failure (HF) is a leading cause of hospitalization and death worldwide. The Steady Movement with Innovating Leadership for Heart Failure (SMILE HF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute HF in South Korea. Methods: This prospective, observational multicenter cohort study was conducted on consecutive patients hospitalized for acute HF in nine university hospitals since September 2019. Enrolment of 2000 patients should be completed in 2024, and follow-up is planned through 2025. Results: Interim analysis of 1,052 consecutive patients was performed to understand the baseline characteristics. The mean age was 69±15 years; 57.6% were male. The mean left ventricular ejection fraction was 39±15%. The prevalences of HF with reduced ejection fraction, HF with mildly reduced ejection fraction, and HF with preserved ejection fraction were 50.9%, 15.3%, and 29.2%. Ischemic cardiomyopathy (CMP) was the most common etiology (32%), followed by tachycardia-induced CMP (12.8%) and idiopathic dilated CMP (9.5%). The prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers/angiotensin receptor/ neprilysin inhibitor, beta-blockers, spironolactone, and sodium-glucose cotransporter-2 inhibitors at discharge were 76.8%, 66.5%, 50.0%, and 17.5%, respectively. The post-discharge 90-day mortality and readmission rates due to HF aggravation were 2.0% and 6.4%, respectively. Our analysis reveals the current state of acute HF in South Korea. Conclusions Our interim analysis provides valuable insights into the clinical characteristics, management, and early outcomes of acute HF patients in South Korea, highlighting the current state and treatment patterns in this population.

Purpose: This study aims to examine the performance of early warning scoring systems regarding adverse events of unanticipated clinical deterioration in complementary and alternative medicine hospitals. Methods: A medical record review of 500 patients from 5-year patient data in two traditional Korean medicine hospitals was conducted. Unanticipated clinical deterioration events included unexpected in-hospital mortality, cardiac arrest, and unplanned transfers to acute-care conventional medicine hospitals. Scores of the Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), and National Early Warning Score 2 (NEWS2) were calculated. Their performance was evaluated by calculating areas under the receiver-operating characteristic curve for the event occurrence. Multiple logistic regression analyses were performed to determine the factors associated with event occurrence. Results: The incidence of unanticipated clinical deterioration events was 1.1% (225/21101). The area under the curve of MEWS, NEWS, and NEWS2 was .68, .72, and .72 at 24 hours before the events, respectively. NEWS and NEWS2, with almost the same performance, were superior to MEWS (p = .009). After adjusting for other variables, patients at low-medium risk (OR = 3.28; 95% CI = 1.02–10.55) and those at medium and high risk (OR = 25.03; 95% CI = 2.78–225.46) on NEWS2 scores were more likely to experience unanticipated clinical deterioration than those at low risk. Other factors associated with the event occurrence included frailty risk scores, clinical worry scores, primary medical diagnosis, prescribed medicine administration, acupuncture treatment, and clinical department. Conclusions The three early warning scores demonstrated moderate-to-fair performance for clinical deterioration events. NEWS2 can be used for early identification of patients at high risk of deterioration in complementary and alternative medicine hospitals. Additionally, patient, care, and system factors need to be considered to improve patient safety.

Purpose: Outcome analysis of urachal cancer (UraC) is limited due to the scarcity of cases and different staging methods compared to urothelial bladder cancer (UroBC). We attempted to assess survival outcomes of UraC and compare to UroBC after stage-matched analyses. Materials and Methods: Total 203 UraC patients from a multicenter database and 373 UroBC patients in single institution from 2000 to 2018 were enrolled (median follow-up, 32 months). Sheldon stage conversion to corresponding TNM staging for UraC was conducted for head-to-head comparison to UroBC. Perioperative clinical variables and pathological results were recorded. Stage-matched analyses for survival by stage were conducted. Results: UraC patients were younger (mean age, 54 vs. 67 years; p < 0.001), with 163 patients (80.3%) receiving partial cystectomy and 23 patients (11.3%) radical cystectomy. UraC was more likely to harbor ≥ pT3a tumors (78.8% vs. 41.8%). While 5-year recurrence-free survival, cancer-specific survival (CSS) and overall survival were comparable between two groups (63.4%, 67%, and 62.1% in UraC and 61.5%, 75.9%, and 67.8% in UroBC, respectively), generally favorable prognosis for UraC in lower stages (pT1-2) but unfavorable outcomes in higher stages (pT4) compared to UroBC was observed, although only 5-year CSS in ≥ pT4 showed statistical significance (p=0.028). Body mass index (hazard ratio [HR], 0.929), diabetes mellitus (HR, 1.921), pathologic T category (HR, 3.846), and lymphovascular invasion (HR, 1.993) were predictors of CSS for all patients. Conclusion Despite differing histology, UraC has comparable prognosis to UroBC with relatively favorable outcome in low stages but worse prognosis in higher stages. The presented system may be useful for future grading and risk stratification of UraC.

BACKGROUND: Mesenchymal stem cells (MSCs) are used for tissue regeneration due to their wide differentiation capacity and anti-inflammatory effects. Extracellular vesicles (EVs) derived from MSCs are also known for their regenerative effects as they contain nucleic acids, proteins, lipids, and cytokines similar to those of parental cells. There are several studies on the use of MSCs or EVs for tissue regeneration. However, the combinatorial effect of human MSCs (hMSCs) and EVs is not clear. In this study, we investigated the combinatorial effect of hMSCs and EVs on cartilage regeneration via co-encapsulation in a hyaluronic-acid (HA)-based hydrogel. METHODS: A methacrylic-acid-based HA hydrogel was prepared to encapsulate hMSCs and EVs in hydrogels. Through in vitro and in vivo analyses, we investigated the chondrogenic potential of the HA hydrogel-encapsulated with hMSCs and EVs. RESULTS: Co-encapsulation of hMSCs with EVs in the HA hydrogel increased the chondrogenic differentiation of hMSCs and regeneration of damaged cartilage tissue compared with that of the HA hydrogel loaded with hMSCs only. CONCLUSION Co-encapsulation of hMSCs and EVs in the HA hydrogel effectively enhances cartilage tissue regeneration due to the combinatorial therapeutic effect of hMSCs and EVs. Thus, in addition to cartilage tissue regeneration for the treatment of osteoarthritis, this approach would be a useful strategy to improve other types of tissue regeneration.

Purpose: Dedicated breast CT is an emerging volumetric X-ray imaging modality for diagnosis that does not require any painful breast compression. To improve the detection rate of weakly enhanced lesions, an adaptive image rescaling (AIR) technique was proposed. Materials and Methods: Two disks containing five identical holes and five holes of different diameters were scanned using 60/100 kVp to obtain single-energy CT (SECT), dual-energy CT (DECT), and AIR images. A piece of pork was also scanned as a subclinical trial. The image quality was evaluated using image contrast and contrast-to-noise ratio (CNR). The difference of imaging performances was confirmed using student’s t test. Results: Total mean image contrast of AIR (0.70) reached 74.5% of that of DECT (0.94) and was higher than that of SECT (0.22) by 318.2%. Total mean CNR of AIR (5.08) was 35.5% of that of SECT (14.30) and was higher than that of DECT (2.28) by 222.8%. A similar trend was observed in the subclinical study. Conclusion The results demonstrated superior image contrast of AIR over SECT, and its higher overall image quality compared to DECT with half the exposure. Therefore, AIR seems to have the potential to improve the detectability of lesions with dedicated breast CT.

KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50 , the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the βancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQspecific agonist in the tissue.

Purpose: To evaluate and compare the feasibilities of magnetic resonance (MR) image-based planning using synthetic computed tomography (sCT) versus CT (pCT)-based planning in helical tomotherapy for prostate cancer. Materials and Methods: A retrospective evaluation was performed in 16 patients with prostate cancer who had been treated with helical tomotherapy. MR images were acquired using a dedicated therapy sequence; sCT images were generated using magnetic resonance for calculating attenuation (MRCAT). The three-dimensional dose distribution according to sCT was recalculated using a previously optimized plan and was compared with the doses calculated using pCT. Results: The mean planning target volume doses calculated by sCT and pCT differed by 0.65% ± 1.11% (p = 0.03). Three-dimensional gamma analysis at a 2%/2 mm dose difference/distance to agreement yielded a pass rate of 0.976 (range, 0.658 to 0.986). Conclusion The dose distribution results obtained using tomotherapy from MR-only simulations were in good agreement with the dose distribution results from simulation CT, with mean dose differences of less than 1% for target volume and normal organs in patients with prostate cancer.

KCNQ family constitutes slowly-activating potassium channels among voltage-gated potassium channel superfamily. Recent studies suggested that KCNQ4 and 5 channels are abundantly expressed in smooth muscle cells, especially in lower urinary tract including corpus cavernosum and that both channels can exert membrane stabilizing effect in the tissues. In this article, we examined the electrophysiological characteristics of overexpressed KCNQ4, 5 channels in HEK293 cells with recently developed KCNQ-specific agonist. With submicromolar EC50 , the drug not only increased the open probability of KCNQ4 channel but also increased slope conductance of the channel. The overall effect of the drug in whole-cell configuration was to increase maximal whole-cell conductance, to prolongate the activation process, and left-shift of the activation curve. The agonistic action of the drug, however, was highly attenuated by the co-expression of one of the βancillary subunits of KCNQ family, KCNE4. Strong in vitro interactions between KCNQ4, 5 and KCNE4 were found through Foster Resonance Energy Transfer and co-immunoprecipitation. Although the expression levels of both KCNQ4 and KCNE4 are high in mesenteric arterial smooth muscle cells, we found that 1 μM of the agonist was sufficient to almost completely relax phenylephrine-induced contraction of the muscle strip. Significant expression of KCNQ4 and KCNE4 in corpus cavernosum together with high tonic contractility of the tissue grants highly promising relaxational effect of the KCNQspecific agonist in the tissue.

We present a rare case of urothelial carcinoma in situ (CIS), which invades the prostate and seminal vesicle (SV). A 70-year-old man underwent transurethral resection of bladder (TURB), and the pathologic examination revealed multiple CIS. Although the patient received intravesical bacillus Calmette-Guerin (BCG) therapy following TURB, recurrence of CIS was confirmed in the bladder and left distal ureter at 3 months following BCG. Radical cystectomy was performed due to BCG-refractory CIS. Microscopically, CIS was found throughout the mucosa of the bladder, left ureter, prostatic duct, and both SVs. Next-generation sequencing revealed significant differences in tumor clonality between bladder and SV CIS cells. Among 101 (bladder CIS) and 95 (SV CIS) somatic mutations, only two were shared, and only one gene (ARHGAP23) was common exon coding region gene. In conclusion, multicentric genetic changes, in line with the field-cancerization effect, may result in SV involvement by CIS of the bladder.