Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study.

BACKGROUND: In the primary analysis of the CLEAR study, lenvatinib plus pembrolizumab significantly improved progression-free survival and overall survival versus sunitinib in patients with advanced renal cell carcinoma (data cutoff Aug 28, 2020). We aimed to assess overall survival based on 7 months of additional follow-up. METHODS: This is a protocol-prespecified updated overall survival analysis (data cutoff March 31, 2021) of the open-label, phase 3, randomised CLEAR trial. Patients with clear-cell advanced renal cell carcinoma who had not received any systemic anticancer therapy for renal cell carcinoma, including anti-vascular endothelial growth factor therapy, or any systemic investigational anticancer drug, were eligible for inclusion from 200 sites (hospitals and cancer centres) across 20 countries. Patients were randomly assigned (1:1:1) to receive lenvatinib (20 mg per day orally in 21-day cycles) plus pembrolizumab (200 mg intravenously every 21 days; lenvatinib plus pembrolizumab group), lenvatinib (18 mg per day orally) plus everolimus (5 mg per day orally; lenvatinib plus everolimus group [not reported in this updated analysis]) in 21-day cycles, or sunitinib (50 mg per day orally, 4 weeks on and 2 weeks off; sunitinib group). Eligible patients were at least 18 years old with a Karnofsky performance status of 70 or higher. A computer-generated randomisation scheme was used, and stratification factors were geographical region and Memorial Sloan Kettering Cancer Center prognostic groups. The primary endpoint was progression-free survival assessed by independent imaging review according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). In this Article, extended follow-up analyses for progression-free survival and protocol-specified updated overall survival data are reported for the intention-to-treat population. No safety analyses were done at this follow-up. This study is closed to new participants and is registered with ClinicalTrials.gov, NCT02811861. FINDINGS: Between Oct 13, 2016, and July 24, 2019, 1417 patients were screened for inclusion in the CLEAR trial, of whom 1069 (75%; 273 [26%] female, 796 [74%] male; median age 62 years [IQR 55-69]) were randomly assigned: 355 (33%) patients (255 [72%] male and 100 [28%] female) to the lenvatinib plus pembrolizumab group, 357 (33%) patients (275 [77%] male and 82 [23%] female) to the sunitinib group, and 357 (33%) patients to the lenvatinib plus everolimus group (not reported in this updated analysis). Median follow-up for progression-free survival was 27·8 months (IQR 20·3-33·8) in the lenvatinib plus pembrolizumab group and 19·4 months (5·5-32·5) in the sunitinib group. Median progression-free survival was 23·3 months (95% CI 20·8-27·7) in the lenvatinib plus pembrolizumab group and 9·2 months (6·0-11·0) in the sunitinib group (stratified hazard ratio [HR] 0·42 [95% CI 0·34-0·52]). Median overall survival follow-up was 33·7 months (IQR 27·4-36·9) in the lenvatinib plus pembrolizumab group and 33·4 months (26·7-36·8) in the sunitinib group. Overall survival was improved with lenvatinib plus pembrolizumab (median not reached [95% CI 41·5-not estimable]) versus sunitinib (median not reached [38·4-not estimable]; HR 0·72 [95% CI 0·55-0·93]). INTERPRETATION: Efficacy benefits of lenvatinib plus pembrolizumab over sunitinib were durable and clinically meaningful with extended follow-up. These results support the use of lenvatinib plus pembrolizumab as a first-line therapy for patients with advanced renal cell carcinoma. FUNDING: Eisai and Merck Sharp & Dohme.

Discovery of BET specific bromodomain inhibitors with a novel scaffold.

Bromodomain and extra-terminal domain (BET) proteins have been considered as potent candidates for anti-cancer drug development. As epigenetic readers, they modulate gene expression by recognizing acetylated lysine residues on histones. Therefore, the pharmacological inhibition of BET proteins has been extensively studied. Herein, we report the novel chemical scaffold of N-(pyridin-2-yl)-1H-benzo[d][1,2,3]triazol-5-amine as BET inhibitors using high-throughput screening assay. Through the analysis of structure-activity relationships, we developed a potent novel compound, which exhibited a better IC50 value about 2-fold compared to iBet762 against the BRD4 bromodomain (BD). The addition of a sulfonyl group to the pyridine ring enhanced the inhibitory activity. Structural studies showed a clear electron density map for the inhibitor and revealed the structural basis for the critical role of the sulfonyl group in the interaction with BRD4.

Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV­201): a multicentre, single-arm, phase 2 trial.

BACKGROUND: Locally advanced or metastatic urothelial carcinoma is generally incurable and has scarce treatment options, especially for cisplatin-ineligible patients previously treated with PD-1 or PD-L1 therapy. Enfortumab vedotin is an antibody-drug conjugate directed at Nectin-4, a protein highly expressed in urothelial carcinoma. We aimed to evaluate the efficacy and safety of enfortumab vedotin in the post-immunotherapy setting in cisplatin-ineligible patients. METHODS: EV-201 is a multicentre, single-arm, phase 2 study of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma previously treated with PD-1 or PD-L1 inhibitors. Cohort 2 included adults (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status score of 2 or less who were considered ineligible for cisplatin at enrolment and who had not received platinum-containing chemotherapy in the locally advanced or metastatic setting. Enfortumab vedotin was given intravenously at a dose of 1·25 mg/kg on days 1, 8, and 15 of every 28-day cycle. The primary endpoint was confirmed objective response rate per Response Evaluation Criteria in Solid Tumours version 1.1 assessed by blinded independent central review. Efficacy and safety were analysed in all patients who received at least one dose of enfortumab vedotin. EV-201 is an ongoing study and the primary analysis is complete. This study is registered with Clinicaltrials.gov, NCT03219333. FINDINGS: Between Oct 8, 2017, and Feb 11, 2020, 91 patients were enrolled at 40 sites globally, of whom 89 received treatment. Median follow-up was 13·4 months (IQR 11·3-18·9). At data cutoff (Sept 8, 2020), the confirmed objective response rate was 52% (46 of 89 patients; 95% CI 41-62), with 18 (20%) of 89 patients achieving a complete response and 28 (31%) achieving a partial response. 49 (55%) of 89 patients had grade 3 or worse treatment-related adverse events. The most common grade 3 or 4 treatment-related adverse events were neutropenia (eight [9%] patients), maculopapular rash (seven [8%] patients), and fatigue (six [7%] patients). Treatment-related serious adverse events occurred in 15 (17%) patients. Three (3%) patients died due to acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome (one [1%] each) within 30 days of first dose and these deaths were considered by the investigator to be related to treatment; a fourth death from pneumonitis occurred more than 30 days after the last dose and was also considered to be related to treatment. INTERPRETATION: Treatment with enfortumab vedotin was tolerable and confirmed responses were seen in 52% of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma who were previously treated with PD-1 or PD-L1 inhibitors. These patients have few treatment options, and enfortumab vedotin could be a promising new therapy for a patient population with a high unmet need. FUNDING: Astellas Pharma Global Development and Seagen.

Efficacy of Biologic Therapies for Eosinophilic Otitis Media: A Systematic Review and Meta-analysis.

Eosinophilic otitis media, first reported in Japan, is a viscous, intractable otitis media often linked to bronchial asthma and chronic rhinosinusitis, characterized by highly viscous middle ear effusion. Its pathological mechanism remains unclear and the condition occasionally does not respond to steroids. It is now recognized as a rare type 2 inflammatory disease and should be treated specifically to enhance quality of life. This systematic review and meta-analysis evaluated the efficacies of biologic treatments. We searched PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to September 2023. We retrieved ear examination findings, otitis media-related and symptom scores, air-bone gaps and hearing thresholds, serum eosinophil, and immunoglobulin E (IgE) levels before and after biologic treatments. Biologics treatment significantly improved subjective otitis media-related scores, compared with control group (standard mean difference (SMD) -1.62; 95% confidence interval (CI) [-2.24; -1.01], I2=54%). Additionally, the serum eosinophil counts and IgE levels significantly decreased (SMD -1.40; 95% CI [-1.99; -0.81], I 2=0%) after 6-12 months of biologic treatments, but the hearing thresholds did not significantly change. There were no significant differences between groups treated with dupilumab and groups treated with other biologics. Biologics treatment for eosinophilic otitis media significantly improved subjective otitis media-related scores and decreased serum eosinophil and IgE levels, but no significant changes in hearing threshold. More randomized cohort studies are needed to confirm the efficacies of biologics in patients with refractory eosinophilic otitis media.

Structurally Reinforced Silicon/Graphene Composite for Lithium-Ion Battery Anodes: Carbon Anchor as a Conductive Structural Support.

Herein, a Si/reduced graphene oxide (rGO)/C microsphere composite is reported, wherein sucrose-derived carbon binds Si nanoparticles (NPs) and rGO to act as a carbon anchor and links neighboring rGO sheets to reinforce the composite structure. In this structurally reinforced Si/rGO/C composite, the electron conduction pathways between rGO and Si NPs were maintained even under large volume changes during repeated charge-discharge processes. Consequently, the Si/rGO/C composite anode exhibited an initial discharge capacity of 1209 mAh g-1 and superior cyclability (92 % retention at 100 cycles), initial coulombic efficiency of 80.5 %, and high-rate capability even at a high C rate (6 C). Furthermore, the change in anode thickness after repeated cycling was negligible, confirming the structural stability imparted by the sucrose-derived carbon binder. A full cell assembled with a LiCoO2 cathode and the Si/rGO/C composite anode remained stable over 200 cycles.

Topology dependent modification of layered double hydroxide for therapeutic and diagnostic platform.

Layered double hydroxide is a family of two-dimensional materials with wide range of compositions. Recently, its ability to accommodate various chemical species and biocompatibility have been attracted in the biomedical applications to develop drug delivery system and nanodiagnostics. In this review, we categorized biomedical approaches of layered double hydroxide with respect to the three topologies of, namely, interlayer space, outer surface with particle edge, and the lattice points. There have been extensive researches on the intercalation of drug or tracing to make use of interlayer space of layered double hydroxide for drug stabilization, sustained release, cellular delivery and etc. Outer surface or edge has been utilized to immobilization of large therapeutic moieties and to attach tracing moiety. Lattice points consisting of various metal species could be utilized for the specific metal species like paramagnetic elements or radioisotopes. Based on these topologies in layered double hydroxide, both the synthetic routes and the achieved functionalities in terms of biomedical application will be discussed.

Dispersion assisted pretreatment for enhanced anaerobic biodegradability and biogas recovery -strategies and applications.

Disperser assisted homogenization is a promising mechanical based disintegration process to improve the substrate biodegradability and biogas recovery from biomass. During dispersion, the extent of liquefaction relies on the dispersion parameters and biomass properties. Hence, assessment of the optimal parameters varies with type of disperser and biomass. Dispersion assisted homogenization of some biomass such as sludge is not only studied in lab scale but also investigated in full scale plants providing positive outcome. For instance, the large-scale investigation of disperser homogenization has attained nearly 40-50 percent increment in bioenergy recovery. However, research gaps in terms of energy and cost efficiency still exists. This review paper outlines the impact of disperser parameters, its efficiency in biomass disintegration and biogas recovery. It has been proposed to combine homogenization process in the bioenergy generation to investigate the energy and cost efficiency of the entire process.

Recent developments in biorefining of macroalgae metabolites and their industrial applications - A circular economy approach.

The macroalgal industry is expanding, and the quest for novel ingredients to improve and develop innovative products is crucial. Consumers are increasingly looking for natural-derived ingredients in cosmetic products that have been proven to be effective and safe. Macroalgae-derived compounds have growing popularity in skincare products as they are natural, abundant, biocompatible, and renewable. Due to their high biomass yields, rapid growth rates, and cultivation process, they are gaining widespread recognition as potentially sustainable resources better suited for biorefinery processes. This review demonstrates macroalgae metabolites and their industrial applications in moisturizers, anti-aging, skin whitening, hair, and oral care products. These chemicals can be obtained in combination with energy products to increase the value of macroalgae from an industrial perspective with a zero-waste approach by linking multiple refineries. The key challenges, bottlenecks, and future perspectives in the operation and outlook of macroalgal biorefineries were also discussed.

Physeal and metaphyseal fractures of the distal radius in pediatric patients

This article aims to summarize the available information and present treatment recommendations. The scope of this discussion is limited to physeal and metaphyseal fractures of the pediatric distal radius.Current Concepts: Pediatric distal radial fractures are common among children and adolescents. The mechanism of injury is usually a fall on an outstretched hand, and fractures typically occur during sports-related activities. Children with distal radial fractures initially present with pain, swelling, and distal forearm deformities. Plain radiographs are essential for evaluating the fracture type and degree of displacement. Complete wrist, forearm, and elbow views should also be assessed, especially for high-energy injuries, to identify ipsilateral fractures. Fractures typically involve the distal radial metaphysis or physis. Metaphyseal fractures are classified as torus, buckle, and bicortical fractures. Most displaced Salter-Harris types I and II and non-displaced metaphyseal fractures can be treated with closed reduction and casting. Operative treatment is recommended if irreducibility or soft-tissue neurovascular compromise is suspected. Operative options include closed reduction, percutaneous pinning, or open reduction, followed by pin or plate fixation. Malunion, nonunion, physeal arrest, ulnocarpal impaction, and nerve injury are possible complications of distal radial fractures in pediatric patients.Discussion and Conclusion: Metaphyseal and physeal fractures of the distal radius are common in children. Most cases are best treated with closed reduction and cast immobilization. Clinicians should be aware of delayed complications and understand how to manage them to ensure successful long-term outcomes.

Clinical Outcomes of Triple Tension Band Wirings in Comminuted Patellar Fracture:A Comparison with Conventional Tension Band Wiring

Purpose@#This study devised triple tension band wirings (TTBW) fixation in patients with comminuted patella fractures to compare the clinical result of TTBW with that of tension band wiring (TBW). @*Materials and Methods@#This study was conducted on 91 patients who had undergone surgery diagnosed with acute patella fracture from January 2011 to December 2016. The study included 51 double TBW patients (Group 1) and 40 patients with TTBW (Group 2). @*Results@#Five out of 51 cases had a loss of reduction and fixation failure in Group 1, and no failure of fracture formation healing occurred in Group 2. Nonunion was noted in one case in Group 1 and no case in Group 2. Eight K-wire migration cases were observed in Group 1, which was not observed in Group 2. Six patients in Group 1 underwent revisional surgery. No patients in Group 2 had a reoperation. As a result of a one-year follow-up after the operation, the mean range of motion of the knee joint in groups 1 and 2 was 128.3°±11.3° and 127.9°±10.8°, respectively. The Lysholm’s scores for groups 1 and 2 were 90.8±4.2 and 90.3±3.8 points, respectively, which was not statistically significant. @*Conclusion@#TTBW is a helpful technique for the surgical treatment of comminuted patella fractures. The TTBW method has less reoperation due to nonunion and fixation failure. After a one-year followup, the clinical results were similar to the conventional TBW method.

The Results of Intramedullary Nailing with Sliding Restriction and Dynamization Method in Treating Intertrochanteric Fractures

Purpose@#To evaluate the results of intramedullary nailing with sliding restriction and dynamization methods in treating intertrochanteric fractures. @*Materials and Methods@#From August 2016 to March 2019, patients aged 65 years and older who underwent intramedullary nailing in treating intertrochanteric fractures were enrolled in this study. The radiological and clinical results were analyzed in 49 patients who had undergone lag screw sliding re-striction and dynamization of the distal interlocking screw method. @*Results@#Forty-seven patients achieved union without complications (95.9%). The mean union period was 6.5 weeks (range, 6-9 weeks). Complications occurred in two patients (4.1%), including the cut through of the lag screw in one patient and varus deformity of more than 10° in the other. The preinjury mean Koval grade was 2.8 (range, 1-7). The mean was 3.3 (range, 1-7) at the final follow-up, and the mean difference was 0.5 (range, 0-2). @*Conclusion@#Intramedullary nailing with a sliding restriction and dynamization method for treating in-tertrochanteric fractures achieved union. The reduction achieved during surgery was maintained with good clinical results. This method is a safe and effective treatment technique for femoral intertrochanteric fractures.

Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Real-World, Retrospective Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The aim of this retrospective study was to evaluate the efficacy of adjuvant cisplatin-based chemotherapy in patients with locally advanced upper tract urothelial carcinoma (UTUC), administered following radical nephroureterectomy. @*Materials and Methods@#Patients with UTUC, arising from renal pelvis or ureter, staged pT3/T4 or N+ were treated with adjuvant chemotherapy following surgery. The chemotherapy consisted of gemcitabine 1,000 mg/m2 on days 1 and 8, cisplatin 70 mg/m2 on day 1. Treatment was repeated every 3 weeks for up to 4 cycles. Endpoints included disease-free survival (DFS), metastasis-free survival (MFS), and safety. @*Results@#Among 89 eligible patients, 85 (95.5%) completed at least 3 cycles of adjuvant chemotherapy. Chemotherapy was well tolerated, the main toxicities being mild-to-moderate gastrointestinal toxic effects and pruritus. With a median follow-up of 37 months, median DFS was 30 months (95% confidence interval, 22 to 39), and the median MFS was not reached. The 3-year DFS and MFS were 44% and 56%, respectively. Multivariate analyses revealed that the main factor associated with DFS and MFS was the lymph node involvement, whereas age, T category, grade, or the primary site of UTUC were not significantly associated with DFS or MFS. @*Conclusion@#Adjuvant cisplatin-based chemotherapy after radical surgery of pT3/T4 or N+ UTUC was feasible and may demonstrate benefits in DFS and MFS. Whether novel agents added to the chemotherapy regimen, as a concurrent combination or maintenance, impacts on survival or reduces the development of metastases remains to be studied.

Does Preoperative Radiation Therapy Performed for Metastatic Spine Cancer at the Cervical Spine Increase Perioperative Complications of Anterior Cervical Surgery?

Background@#Radiation therapy (RT) performed before anterior cervical spine surgery (ACSS) may cause fascial plane fibrosis, decreased soft-tissue vascularity, and vertebral body weakness, which could increase the risk of esophageal and major vessel injuries, wound complications, and construct subsidence. Therefore, this study aimed to evaluate whether preoperative RT performed for metastatic spine cancer (MSC) at the cervical spine increases perioperative morbidity for ACSS. @*Methods@#Forty-nine patients who underwent ACSS for treatment of MSC at the cervical spine were retrospectively reviewed. All the patients underwent anterior cervical corpectomy via the anterior approach. Patient demographics, surgical factors, operative factors, and complications were recorded. Results of patients who were initially treated with RT before ACSS (RT group) were compared with those who did not receive RT before ACSS (non-RT group). @*Results@#Eighteen patients (36.7%) were included in the RT group, while the remaining 31 (63.3%) were included in the nonRT group. Surgery-related factors, including operation time (p = 0.109), estimated blood loss (p = 0.246), amount of postoperative drainage (p = 0.604), number of levels operated (p = 0.207), and number of patients who underwent combined posterior fusion (p = 0.768), did not significantly differ between the 2 groups. Complication rates, including esophageal injury, dural tear, infection, wound dehiscence, and mechanical failure, did not significantly differ between the RT and non-RT groups. Early subsidence was significantly greater in the non-RT group compared to that in the RT group (p = 0.012). @*Conclusions@#RT performed before surgery for MSC does not increase the risk of wound complication, mechanical failure, or vital structure injury during ACSS. The surgical procedural approach was not complicated by previous RT history. Therefore, surgeons can safely choose the anterior approach when the number of levels or location of MSC favors anterior surgery, and performing a posterior surgery is unnecessary due to a concern that previous RT may increase complication rates of ACSS.

Validation of a Korean Version of the Short UPPS-P Impulsive Behavior Scale for Children

Objective@#Impulsivity is a multifaceted construct that plays an important role in various problem behaviors in children and adolescents. The purpose of this study was to validate a Korean version of the short UPPS-P Impulsive Behavior Scale for Children. @*Methods@#Participants were 330 children (166 female) from 2 elementary schools in Korea and 94 attention deficit hyperactivity disorder (ADHD) children (23 female) from two major hospitals. The Korean short UPPS-P Impulsive Behavior Scale for Children (UPPS-P-C) (20 items), Child Behavior Checklist for Ages 6–18 (CBCL 6–18), and Barratt Impulsiveness Scale-11 (BIS-11) were administered. 107 children from the control group were retested 6 months later. @*Results@#Confirmatory factor analysis (CFA) conducted in the control group supported a 5-factor hierarchical model in which 1) positive and negative urgency factors are loaded on a higher-order factor of general urgency; 2) lack of perseveration and lack of premeditation factors are loaded on a higher-order factor of lack of conscientiousness; and 3) sensation seeking remained as a separate dimension. Reliability analysis demonstrated that the 5 factors of the Korean short UPPS-P-C had acceptable internal consistency and test-retest reliability. Lack of premeditation and lack of perseveration subscales showed significant correlations with measures of problem behaviors in CBCL and all the subscales were correlated with the BIS-11. The ADHD group showed significantly higher scores in lack of premeditation, lack of perseveration, positive urgency, and negative urgency subscales. @*Conclusion@#This study indicates that the Korean version of short UPPS-P-C has adequate reliability and validity. It may be a valid tool to assess impulsivity of healthy children as well as ADHD.

Adiponectin restores the obesity-induced impaired immunomodulatory function of mesenchymal stromal cells via glycolytic reprogramming

Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells (MSC). However, it remains unclear what drives the compromised potency of obese MSC. In this study, we examined the involvement of adiponectin, an adipose tissue-derived hormone, in obesity-induced impaired therapeutic function of MSC. Diet-induced obesity leads to a decrease in serum adiponectin, accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC (ADSC). Interestingly, priming with globular adiponectin (gAcrp) improved the immunomodulatory potential of obese ADSC. Similar effects were also observed in lean ADSC. In addition, gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis. Mechanistically, while obesity inhibited the glycolytic capacity of MSC, gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1α axis. These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

Neoadjuvant Cisplatin-Based Chemotherapy Followed by Selective Bladder Preservation Chemoradiotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder: Post Hoc Analysis of Two Prospective Studies / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT. @*Materials and Methods@#The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT. @*Results@#Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976). @*Conclusion@#The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.

Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression

Background/Aims@#Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. @*Methods@#Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. @*Results@#After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. @*Conclusions@#We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Analysis of Characteristics and Risk Factors of Patients with Single Gastric Cancer and Synchronous Multiple Gastric Cancer among 14,603 Patients

Background/Aims@#Synchronous multiple gastric cancer (SMGC) accounts for approximately 6% to 14% of gastric cancer (GC) cases. This study aimed to identify risk factors for SMGC. @*Methods@#A total of 14,603 patients diagnosed with GC were prospectively enrolled. Data including age, sex, body mass index, smoking, alcohol consumption, family history, p53 expression, microsatellite instability, cancer classification, lymph node metastasis, and treatment were collected. Risk factors were analyzed using logistic regression analysis between a single GC and SMGC. @*Results@#The incidence of SMGC was 4.04%, and that of early GC (EGC) and advanced GC (AGC) was 5.43% and 3.11%, respectively. Patients with SMGC were older (65.33 years vs 61.75 years, p<0.001) and more likely to be male. Lymph node metastasis was found in 27% of patients with SMGC and 32% of patients with single GC. Multivariate analysis showed that SMGC was associated with sex (male odds ratio [OR], 1.669; 95% confidence interval [CI], 1.223 to 2.278; p=0.001), age (≥65 years OR, 1.532; 95% CI, 1.169 to 2.008; p=0.002), and EGC (OR, 1.929; 95% CI, 1.432 to 2.600; p<0.001). Survival rates were affected by Lauren classification, sex, tumor size, cancer type, distant metastasis, and venous invasion but were not related to the number of GCs. However, the survival rate of AGC with SMGC was very high. @*Conclusions@#SMGC had unique characteristics such as male sex, older age, and EGC, and the survival rate of AGC, in which the intestinal type was much more frequent, was very good (Trial registration number: NCT04973631).

Joint Replacement Surgery in Patients with Rheumatoid Arthritis in South Korea:Analysis of a Large National Database

Background@#We aimed to investigate the current trend of joint replacement surgery incidence in patients with rheumatoid arthritis (RA) in South Korea and to compare the incidence of joint replacement surgery in each affected joint. @*Methods@#We performed this big data analysis to investigate the current trend of joint replacement surgery incidence in patients with RA in South Korea and to compare the incidence of joint replacement surgery in each affected joint. This retrospective study was based on data from the Korea National Health Insurance claims database. @*Results@#The prevalence of RA increased every year (0.13% in 2008, 0.25% in 2016). The number of newly diagnosed patients increased from 29,184 in 2010 to 38,347 in 2016. The incidence rate of joint replacement surgery in patients with RA increased from 0.72% in 2010 to 4.03% in 2016. The knee (68.3%) was the most commonly replaced joint. The relative risk (RR) of additional joint replacement surgery was highest for the shoulder joint (RR,1.454; 95% confidence interval, 0.763–2.771). The median time from diagnosis to surgery was the shortest in the elbow joint (379 days) and the longest in the shoulder joint (955 days). The median time for each joint was short in order of the elbows, ankles, hips, knees, and shoulders (p < 0.01). @*Conclusions@#The most frequently and initially replaced joints were different, but the prevalence and incidence of RA, as well as those of joint replacement surgery, have recently increased in South Korea. Joint replacement surgery in RA was the highest for the knee joint. The median time from diagnosis to surgery was shortest for the elbow, followed by the ankle, hip, knee, and shoulder. Regardless of whether patients are symptomatic, evaluation of large joints such as the knee, elbow, ankle, and hip should be considered from an early stage.

Combined PCL and PLC Reconstruction Improves Residual Laxity in PCL Injury Patients with Posterolateral Knee Laxity Less Than Grade III

Purpose@#To compare the short-term clinical and radiologic outcomes of combined posterior cruciate ligament (PCL) and posterolateral complex (PLC) reconstruction to those of isolated PCL reconstruction (PCLR) for patients with posterolateral knee laxity less than grade III. @*Materials and Methods@#We retrospectively reviewed 49 patients (51 knees) who underwent PCLR between January 2008 and December 2015. Patients with a minimum follow-up of 24 months were included and divided into two groups (group A, isolated PCLR; group B, combined PCL and PLC reconstruction). Clinical outcomes were evaluated as the International Knee Documentation Committee (IKDC) subjective, Lysholm, and Tegner activity scale scores. Radiologic outcomes were also assessed using the side-to-side differences in posterior tibial translation via stress radiographs. @*Results@#A total of 30 cases were analyzed. There were no significant differences in the Lysholm and Tegner activity scale scores between the two groups preoperatively and at the final follow-up. However, group B showed a higher IKDC subjective score compared to group A at the final follow-up (group A, 72.8±8.9; group B, 77.7±10.1; p<0.05). Regarding the radiologic outcomes, group B also showed a significantly less side-to-side difference in posterior tibial translation compared to group A at the final follow-up (group A, 4.8±2.3 mm; group B, 3.8±2.1 mm; p<0.05). @*Conclusion@#Combined PCL and PLC reconstruction resulted in improved clinical and radiologic outcomes than isolated PCLR in patients who have less than grade III posterolateral laxity of the knee. In cases of PCL rupture with ambiguous PLC injury, combined PCL and PLC reconstruction may help to improve posterior residual laxity of the knee.