Clinical trials

Acute kidney injury (AKI) is a frequent and serious complication after cardiac surgery, including off-pump coronary artery bypass (OPCAB). Because AKI is diagnosed on the basis of serum creatinine, which rises 1 to 2 days after the actual renal insult, early detection and timely intervention remain difficult. Near-infrared spectroscopy (NIRS) allows non-invasive and continuous measurement of regional tissue oxygen saturation, but the effective penetration depth of commercially available devices is only approximately 2 to 2.5 cm. In most adults the renal cortex lies deeper than this, so the signal obtained from a flank sensor may originate largely from the abdominal wall musculature rather than from renal parenchyma. This limitation may explain the inconsistent association between renal regional oxygen saturation (renal rSO2) and AKI reported so far. The erector spinae muscle at the level of the renal hilum lies within 2 cm of the skin in most patients and is supplied by the lumbar arteries and by vessels adjacent to the renal hilum. Erector spinae muscle regional oxygen saturation (ESrSO2) may therefore provide a technically more reliable NIRS signal that reflects perfusion of a vascular territory close to that of the kidney, particularly during the transient low cardiac output state induced by mechanical displacement of the heart for coronary anastomosis during OPCAB. This single-center prospective observational cohort study will enroll 138 adult patients scheduled for elective OPCAB at Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea. ESrSO2 and renal rSO2 will be measured continuously with an INVOS oximeter from before anesthetic induction until the end of surgery, in addition to cerebral rSO2, which is part of standard care at the participating institution. The ESrSO2 and renal rSO2 channels will be physically masked on the monitor display during surgery, no alarms will be set for these two channels, and their values will not be used for any intraoperative clinical decision. The recorded data will be extracted after surgery using the INVOS Analytics Tool. Apart from placement of the additional NIRS sensors and a brief pre-induction ultrasound measurement of tissue depth, no study-specific procedure, laboratory test, or imaging study will be performed, and all anesthetic, surgical, and postoperative care will follow the standard institutional protocol. The primary objective is to identify which ESrSO2-derived variable best predicts postoperative AKI, defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria within 7 days after surgery. The candidate variables are the baseline value, the intraoperative nadir, the area under the threshold (AUT), and the duration under the threshold below absolute values of 60%, 55%, and 50% and below 80% of the baseline value, calculated separately for the period before cardiac displacement and for the cardiac displacement period. Secondary objectives are to assess whether the selected ESrSO2 variable provides independent and incremental predictive information beyond a pre-specified baseline risk model, to compare the predictive performance of ESrSO2 with that of cerebral rSO2 and renal rSO2, and to evaluate the prediction of severe AKI (KDIGO stage 2 to 3) and persistent AKI (lasting 48 hours or longer). If ESrSO2 proves to be a useful early marker of AKI, it could allow real-time, non-invasive identification of patients at high risk during surgery and provide a basis for future trials of renal protective strategies.

Upper tract urothelial carcinoma (UTUC) is difficult to stage accurately because cross-sectional imaging and ureteroscopic biopsy may not reliably demonstrate muscular or periureteral invasion. This exploratory study evaluates whether a 60-MHz OptiCross HD intravascular ultrasound (IVUS) catheter can be safely introduced into the renal pelvis or ureter during planned surgery and provide intraluminal images that correspond to the final pathologic T stage. Fifteen adults with suspected or confirmed UTUC who are already scheduled for radical nephroureterectomy (RNU) will undergo one IVUS examination immediately before surgery. The IVUS result will not alter the planned treatment. Three independent reviewers who are blinded to clinical and pathologic information will assess invasion depth and image quality. IVUS-based T stage will be compared with postoperative pathology. Technical success, visualization of ureteral wall layers and lesion boundaries, and adverse events will also be evaluated through 3 months after surgery.

Comparison of * Biolimus-eluting stent, Biomatrix, or Biomatrix Flex stent, Biosensors, Singapore * Everolimus-eluting stent, Xience V, or Xience Prime, or Xience Xpedition stent, Abbott, USA * Zotarolimus-eluting stent, Endeavor Resolute, or Endeavor Resolute Integrity stent Medtronic, USA in patients with coronary artery disease treated with percutaneous coronary intervention

This clinical trial is an open-label, multicenter, prospective phase 2 clinical trial targeting pediatric leukemia patients of infant age. The goal is to improve survival rates by varying the presence or absence of chemotherapy and hematopoietic stem cell transplantation based on genetic characteristics at the time of diagnosis and minimal residual disease (MRD) values measured by various methods after treatment. In addition, by clearly defining the patient group that requires hematopoietic stem cell transplantation, it is expected that the role of hematopoietic stem cell transplantation in infantile leukemia, for which there have been various guidelines for hematopoietic stem cell transplantation, can be confirmed. Additionally, due to the characteristics of infants, this study aim to identify long-term sequelae or prognosis related to treatment by prospectively collecting side effect data related to treatment during and after treatment.

This exploratory pilot randomized controlled trial evaluates whether a HeartMate application-based remote patient monitoring (RPM) and digital cardiac rehabilitation program improves cardiovascular, functional, and psychological outcomes in patients with cardiac disease. A total of 200 participants with cardiovascluar disease requiring rehabilitation are randomly assigned in a 1:1 ratio to an intervention group or a control group. The intervention group uses the HeartMate app-based remote cardiac rehabilitation program for 6 weeks, including a daily heart check using smartphone remote photoplethysmography (rPPG), aerobic and resistance exercise, breathing training, and a cognitive-behavioral 'mind' program, with weekly remote coaching. The control group receives usual outpatient care and lifestyle education materials, with the app installed only for rPPG measurement so that digital-biomarker measurement is identical across groups. Clinical assessments (6-minute walk distance, grip strength, blood pressure, blood lipids and metabolic markers), questionnaires (SF-12, PHQ-9, GAD-7, KOSS-24), and digital biomarkers (rPPG-derived heart rate, heart rate variability, respiration, activity) are collected at baseline and at 6 weeks. The primary outcome is the between-group difference in the change in 6-minute walk distance from baseline to 6 weeks. Because this is an exploratory pilot, the results are intended to estimate the effect size and variance for a future definitive randomized controlled trial, and to assess the validity of digital biomarkers as well as the safety, feasibility, and adherence of the program.

Patent foramen ovale (PFO) is a congenital interatrial communication present in about one quarter of the general population and is recognized as a major cause of cryptogenic stroke. Percutaneous PFO closure reduces recurrent stroke, but a residual right-to-left shunt persists in 20 to 40 percent of patients after device implantation. Long-term data on device performance, the evolution of residual shunt over time, new-onset atrial fibrillation and other prognostic factors remain limited. This single-center registry evaluates the long-term efficacy and safety of percutaneous PFO closure and identifies the clinical, anatomical, procedural and pharmacological factors associated with clinical and echocardiographic outcomes. The registry combines a retrospective cohort of patients treated at Severance Hospital between 2010 and March 2026 with a prospective registry extension that enrolls patients undergoing PFO closure after institutional review board approval, with follow-up for up to 119 months. Clinical outcomes include recurrent ischemic stroke or transient ischemic attack, all-cause death, device-related complications and new-onset atrial fibrillation. Echocardiographic outcomes are assessed by serial agitated saline transthoracic echocardiography, which allows the presence, grade and longitudinal trajectory of residual shunt to be characterized.

The goal of this clinical trial is to learn whether a wearable monitoring system can help adults who have had a stroke get more out of a home exercise program. The system tracks how participants walk and move, then gives them feedback. Researchers want to know if this feedback improves walking, thinking and memory, and daily activity. The wearable monitoring system has three parts: A shoe insole sensor that measures how a person walks A wrist band that tracks daily activity, like a fitness watch A mobile app that gives feedback and lets participants report how they feel The main questions this study aims to answer are: Does feedback from the wearable system improve physical function, thinking and memory, and daily activity during a home exercise program? How satisfied are participants with using the wearable system? Researchers will compare two groups. Both groups do the same home exercise program for 6 weeks. One group uses the wearable system and gets feedback. The other group does the program without the wearable system or feedback. This comparison shows whether the feedback itself makes a difference. Who can take part: adults who have had a stroke and \[key eligibility in plain words, e.g., "can walk a short distance with or without help"\]. The study plans to enroll about \[number\] participants. Participants in the wearable group will: Get an insole sensor, a wrist activity tracker, and access to a mobile app Learn a home exercise program from the study team Wear the insole sensor and activity tracker while exercising at home for 6 weeks Use the app to see their feedback and report daily health information Complete a survey about their experience at the end Participants in the comparison group will: Do the same home exercise program for 6 weeks, without the wearable system or feedback.

Patients with diffuse large B-cell lymphoma (DLBCL) who are primary refractory to first-line R-CHOP therapy or relapse within 12 months after R-CHOP have a poor prognosis and limited treatment options. Conventional salvage chemotherapy has limited efficacy, and CAR-T cell therapy may be limited by manufacturing time, accessibility, and patient condition. Therefore, an immediately available, chemotherapy-free treatment strategy that may reduce the cumulative toxicity of conventional cytotoxic chemotherapy is needed. Polatuzumab vedotin is a CD79b-targeted antibody-drug conjugate that delivers a cytotoxic agent to malignant B cells, and glofitamab is a CD20×CD3 bispecific antibody that activates T cells and induces immune-mediated antitumor activity. The combination of these two agents may provide complementary antitumor effects through direct tumor cell killing and T-cell-mediated immune response. This single-arm, open-label, phase 2 study will evaluate the efficacy and safety of polatuzumab vedotin in combination with glofitamab in patients with DLBCL who are primary refractory to or relapse within 12 months after first-line R-CHOP therapy. Approximately 47 participants will be enrolled. The primary endpoint is the complete response rate at the end of treatment, as assessed by the investigator according to Lugano 2014 criteria.

Patients with diabetes are at increased risk of perioperative glycemic disturbances due to preoperative fasting, the surgical stress response, and the use of insulin or oral hypoglycemic agents. Hypoglycemia, in particular, is an important clinical concern associated with neurological injury and cardiovascular complications. In routine practice, intraoperative glucose monitoring often relies on intermittent fingerstick testing or blood gas analysis, and these intermittent methods may fail to detect hypoglycemic episodes that occur during and immediately after surgery. Continuous glucose monitoring (CGM), which estimates glucose concentrations from interstitial fluid, allows continuous tracking of glycemic trends and may provide a more precise assessment of glycemic variability and hypoglycemia in the perioperative period. Although current guidelines recommend periodic intraoperative glucose measurement in patients with diabetes-especially those receiving insulin-glucose monitoring is frequently omitted during relatively short and stable ophthalmic procedures such as vitrectomy. Because vitrectomy is commonly performed in patients with diabetes, perioperative hypoglycemia in this population may go undetected. This is a single-center, prospective, observational cohort study conducted in patients with diabetes undergoing pars plana vitrectomy (TPPV). A masked CGM device (FreeStyle Libre 2®, an approved continuous glucose monitor) is applied for observational purposes only and does not influence clinical care. The sensor is placed on the upper arm before surgery. After an approximately one-hour warm-up period, glucose data are collected at 15-minute intervals from the completion of CGM warm-up until discharge from the post-anesthesia care unit (PACU); this interval defines the perioperative period for data collection. Throughout this period the CGM operates in a masked mode-no reader is provided, the device is not linked to the participant's smartphone, and alarms are disabled-so that real-time glucose values are not displayed to clinicians or participants. All glycemic management follows the existing standard of care based on point-of-care testing (POCT), and CGM data do not contribute to clinical decision-making. After all participants have completed data collection, CGM data are unblinded and analyzed. The primary objective is to estimate the incidence of perioperative hypoglycemia, defined as a CGM glucose value below 70 mg/dL (Level 1), during the perioperative period. Secondary objectives include the incidence of clinically significant hypoglycemia (below 54 mg/dL, Level 2); indices of glycemic variability (Time Below Range, maximum and minimum glucose, and glucose excursion); identification of clinical risk factors associated with perioperative hypoglycemia (such as age, diabetes characteristics, HbA1c, insulin use, fasting duration, and operative time); the exploratory association between perioperative hypoglycemia and postoperative ophthalmic outcomes (changes in best-corrected visual acuity and ophthalmic complications such as recurrent vitreous hemorrhage, retinal redetachment, elevated intraocular pressure, and the need for additional procedures); and an exploratory, opportunistic concordance analysis between standard-of-care POCT glucose values and time-matched CGM values (within ±5 minutes). Hypoglycemia is classified according to ADA/Danne et al. criteria. Eligible participants are adults aged 19 years or older with diabetes who are scheduled for vitrectomy and able to provide written informed consent. Participants are excluded if CGM sensor placement is not feasible, if they have a known sensor allergy, if valid data cannot be obtained, or if voluntary informed consent is not possible. Based on the institution's monthly surgical volume and the estimated proportion of patients with diabetes, a target enrollment of 85 participants over a 12-month study period is considered feasible. Postoperative ophthalmic outcomes are assessed using medical records from routine outpatient follow-up visits (for example, at approximately one week and one to three months after surgery) without any additional study-specific visits. Because the primary aim is to estimate the incidence of perioperative hypoglycemia, ophthalmic outcomes and POCT-CGM concordance are analyzed as exploratory endpoints. This study aims to characterize the limitations of current perioperative glucose monitoring strategies and to provide foundational data for future risk-based monitoring strategies and CGM-based interventional research.

This study aims to compare the operator's radiation exposure between left distal radial access (LDRA) and right transradial access (RTRA) in patients undergoing percutaneous coronary intervention (PCI).

The purpose of this study was to investigate the effect of pitavastatin or pitavastatin and ezetimibe combination therapy on glucose metabolism compared to atorvastatin in patients with atherosclerotic cardiovascular disease with metabolic syndrome.

The clinical efficacy of nivolumab for locally advanced nasopharyngeal carcinoma patients with residual disease after standard chemoradiotherapy is not known. In this study, we aim to investigate the role of nivolumab in locally advanced NPC after chemoradiotherapy the safety profile and antitumor activity of the anti-programmed death 1 (PD-1) receptor monoclonal antibody, nivolumab after in patients with advanced nasopharyngeal carcinoma

This is a multicenter, single-arm, phase 2 clinical trial designed to evaluate the clinical efficacy of combination therapy with zanzalintinib and pembrolizumab in patients with locally advanced intermediate- to high-risk, high-risk, or resectable metastatic clear cell renal cell carcinoma. The neoadjuvant treatment period consists of a total of 6 cycles; pembrolizumab is administered every 3 weeks, and zanzalintinib is administered orally once daily. A drug washout period of at least 21 days is required prior to the last dose before surgery. Surgery will be performed after completion of the neoadjuvant treatment and following a drug washout period of at least 21 days. The adjuvant treatment period begins at least 28 days after surgery, and pembrolizumab is administered every 3 weeks for a total of 11 cycles. Radiologic response assessments are conducted at predefined time points during the neoadjuvant period, and pathologic response is evaluated using resected tissue obtained at the time of surgery. * Study duration: Approximately 30 months (18 months for enrollment + 12 months for treatment and follow-up) * Planned sample size: 48 patients (including an estimated 10% dropout rate) Tumor size and disease stage will be assessed using baseline imaging performed prior to treatment, and tumor response will be evaluated through predefined scheduled imaging assessments conducted during treatment. Tumor response will be evaluated during treatment via imaging at regular intervals per cycle. Surgery will be scheduled after the completion of 6 cycles, following a minimum 21-day washout period (±7 days at the investigator's discretion). If postoperative recovery is adequate (at least 28 days, ±14 days at the investigator's discretion), adjuvant Pembrolizumab treatment will commence.

Background: Radical gastrectomy causes moderate-to-severe pain during the first 48 hours after surgery. Opioids are effective but carry adverse effects and risks of prolonged use, so ERAS-based care recommends multimodal analgesia. Acetaminophen is the most commonly used non-opioid analgesic in gastrectomy patients; adding ibuprofen as a fixed-dose combination has shown improved analgesia and opioid-sparing effects compared with acetaminophen alone in other surgical populations, but direct evidence in gastrectomy patients is limited. Objective: To evaluate whether scheduled administration of an acetaminophen-ibuprofen fixed-dose combination (Maxigesic® IV) is superior to acetaminophen alone for pain relief after radical gastrectomy, with exploratory assessment of cost-effectiveness and of differences in analgesic efficacy according to genetic polymorphisms. Hypothesis: When given on an identical scheduled regimen, the acetaminophen-ibuprofen fixed-dose combination produces significantly lower pain scores (NRS) over the first 48 postoperative hours than acetaminophen alone (superiority). Study plan: This is a phase IV, multicenter, double-blind, randomized controlled trial in which 160 gastric cancer patients scheduled for minimally invasive radical gastrectomy (80 per arm) are randomized 1:1 with stratification by institution. In both arms, the assigned drug is given as a 15-minute intravenous infusion every 6 hours, starting 30 minutes before the end of surgery through 48 hours postoperatively. The primary endpoint is the between-group difference in the time-weighted average (TWA) of repeatedly measured resting and active NRS over 48 hours, analyzed using a mixed model for repeated measures (MMRM); secondary endpoints include opioid consumption (MME), the Quality of Recovery score (QoR-15K), the incidence of chronic postsurgical pain (CPSP), and in-hospital costs.

Currently, the optimal antithrombotic therapy after transcatheter aortic valve replacement (TAVR) remains still unknown., The purpose of the study is to compare aspirin versus clopidogrel monoantiplatelet therapy for preventive effect on leaflet thrombosis in patients undergoing TAVR for severe aortic stenosis. This study is designed as a prospective, multicenter, open label, randomized controlled study. Eligible patients will be randomized to aspirin or clopidogrel monotherapy after TAVR. Patients will have dual antiplatelet therapy of aspirin 100 mg and clopidogrel 75 mg for 4 weeks after TAVR and then subsequent monoantiplatelet therapy of either aspirin 100 mg or clopidogrel 75 mg according to the randomization. Leaflet thrombosis will be assessed with cardiac computed tomography (CT) and transthoracic echocardiography at 3 months after TAVR. Patients will be clinically followed for 6 months. The primary endpoint is the Incidence of leaflet thrombosis on cardiac CT at 3 months.

The ULTRA-CKD trial is a prospective, randomized, open-label, multicenter trial designed to compare the efficacy and safety of moderate-intensity statin plus ezetimibe combination therapy versus high-intensity statin monotherapy in patients with chronic kidney disease (CKD) and concomitant atherosclerotic cardiovascular disease (ASCVD). Patients with CKD are at very high risk for ASCVD. In this population, it is important to establish a lipid-lowering strategy that optimizes cardiovascular outcomes while ensuring long-term safety. While high-intensity statins are generally considered as initial treatment option for secondary prevention, the optimal strategy for CKD patients remains to be clinicaly defined. This study aims to evaluate whether the combination of moderate-intensity statin and ezetimibe is non-inferior to high-intensity statin monotherapy in terms of 3-year composite of major adverse cardiovascular events.

This clinical trial is designed to compare and evaluate the efficacy and safety of the combination therapy of Lurbinectedin plus Paclitaxel (Combination Arm) versus Paclitaxel monotherapy (Monotherapy Arm) in patients with extensive-stage small-cell lung cancer whose disease has progressed after first-line chemotherapy.

This prospective, single-center, single-arm pivotal clinical trial is designed to evaluate the accuracy of blood pressure measurements obtained using the HiCardi M350 patient monitor compared with measurements obtained using an auscultatory sphygmomanometer. The study will enroll adult volunteers aged 19 years or older, including participants needed to satisfy the blood pressure distribution requirements of ISO 81060-2:2018. The planned enrollment is 100 participants, considering the ISO 81060-2:2018 minimum requirement of 85 participants and an estimated dropout rate of approximately 15%. The study is also designed to obtain at least 255 valid paired blood pressure values. After written informed consent, participants will undergo screening assessments, including demographics, vital signs, medical and surgical history, prior and concomitant medications, pregnancy testing for women of childbearing potential, bilateral arm circumference measurement, eligibility assessment, and adverse event assessment. On the blood pressure test day, eligibility will be reconfirmed, an enrollment number will be assigned, HiCardi M350 calibration will be performed, and blood pressure measurements will be obtained using both HiCardi M350 and the reference auscultatory method. The primary effectiveness endpoint is the difference between systolic and diastolic blood pressure values measured by HiCardi M350 and the reference sphygmomanometer under resting conditions. Accuracy will be evaluated according to ISO 81060-2:2018 using Criteria 1 and Criteria 2. Safety will be evaluated based on adverse events, adverse device effects, serious adverse events, serious adverse device effects, unanticipated adverse device effects, and device deficiencies.

Patients hospitalized with cardiovascular disease require timely detection of clinical deterioration to prevent adverse outcomes. Standard inpatient care relies on intermittent nursing vital-sign measurements performed every 4 to 8 hours, which can miss hemodynamic or arrhythmic events occurring between measurements. This trial evaluates whether digital wearable-based monitoring - wireless continuous measurement of vital signs and electrocardiography with a real-time alerting system - reduces major adverse cardiovascular events (MACE) compared with standard intermittent monitoring in patients hospitalized for cardiovascular disease. The trial uses a stepped-wedge cluster-randomized design in which four inpatient ward zones (clusters) are sequentially transitioned from standard care to wearable monitoring over five periods.

Those studies demonstrate strong rationale to combine a multikinase inhibitor targeting VEGFR, PDGFR with mTOR inhibitor. Moreover, another multi-targeted TKI, lenvatinib monotherapy showed promising activity in osteosarcoma. Therefore, clinical trial with Lenvatinib in combined with everolimus is ongoing for solid tumors (NCT03245151). Considering lenvatinib and everolimus (18 mg/day and 5 mg/day) already approved as standard treatment for renal cell carcinoma based on the powerful ORR, PFS, and OS14, these noteworthy findings advance the treatment paradigm for bone sarcoma patients. Because all those trials for sarcoma were done in the absence of a control group, based on such clinical studies, a confirmatory trial comparing mTOR inhibitor and a multi-targeted tyrosine kinase inhibitor (multi-TKI) combination versus monotherapy is essential. Therefore, we planned to conduct the randomized phase II trial of everolimus in combination with lenvatinib for advanced/metastatic bone sarcomas. In addition, we will explore predictive biomarkers by repeated biopsies and blood samplings during the treatment.

This is a single-arm, exploratory phase I clinical trial evaluating the safety and efficacy of ultra-hypofractionated carbon ion radiotherapy (CIRT) in 6 fractions compared to the conventional 12-fraction regimen in patients with low- and intermediate-risk localized prostate cancer. A total of 20 patients will be enrolled sequentially and treated with CIRT at 7 GyE per fraction, delivered twice weekly on alternating days, for a total of 6 fractions (total prescribed dose: 42 GyE). Androgen deprivation therapy for 6 months will be administered concurrently in patients classified as unfavorable intermediate-risk. The primary endpoint is the incidence of acute treatment-related toxicity of Grade 3 or higher per CTCAE v5.0 occurring within 90 days after completion of CIRT. Secondary endpoints include the incidence of late toxicity, biochemical relapse-free survival (bRFS), and quality of life assessed by EPIC-26 and IPSS questionnaires. Patients will undergo scheduled follow-up visits for 2 years after treatment completion, followed by long-term follow-up through electronic medical record review up to 5 years.

Exercise echocardiography is a widely used non-invasive test that evaluates cardiac structure and function during physical stress. It provides important information on myocardial ischemia, cardiac performance, hemodynamic responses, and exercise capacity in patients with a broad range of heart diseases. However, real-world prospective data integrating exercise echocardiographic findings across both ischemic and non-ischemic heart disease remain limited. This prospective observational registry aims to systematically collect clinical, exercise, and echocardiographic data from patients undergoing clinically indicated exercise echocardiography. The registry includes patients with suspected or established ischemic heart disease as well as those with non-ischemic cardiac conditions, such as cardiomyopathies, heart failure, valvular heart disease, and exercise-related symptoms. The collected data will be used to evaluate exercise-induced changes in cardiac structure and function, identify phenotypes associated with adverse clinical outcomes, and improve risk stratification in routine clinical practice. The registry is observational in nature and does not alter standard clinical care.

This study aims to evaluate and compare the degree of alcohol reduction between high-risk drinkers who use a motivational interviewing-based conversational agent (chatbot) application for four weeks and those in the control group who do not use the application, in order to verify its clinical effectiveness.

Combination treatment of Durvalumab with chemoradiotherapy is ongoing for head/neck cancer, renal cell carcinoma, melanoma, and non-small cell lung cancer (NCT02318771) and pancreatic cancer (NCT02305186).Combining Durvalumab with neoadjuvant chemoradiotherapy is a promising strategy to improve clinical outcome in stage III lung cancer. Using serial biopsied and surgically resected fresh tissue through the novel/high-throughput RNA sequencing technologies, we want to identify the change immune signature in tumor microenvironment of NSCLC patients after Durvalumab treatment. With hypothesis that PD-1 inhibitor as a component of neoadjuvant chemoradiotherapy followed by surgery could increase complete pathologic response rate and disease free survival, and overall survival, we suggest adding Durvalumab to neoadjuvant chemoradiation in stage II/III resectable NSCLC. And with immune marker study using FACS, whole exome sequencing, or RNAsequencing, we can find the potential predictive biomarker for anti-PD-L1 blockade. And in this study, we can get "whole" surgical specimen not biopsy sample after Durvalumab treatment so the analysis for immune marker, tumor microenvironment, and various tumor infiltrating immune cells and their changes will be available.

Objective: The purpose of this study is to determine if there is a difference in the recurrence rate of atrial fibrillation (AF) between a group of patients with AF and heart failure undergoing catheter ablation who are administered the SGLT2 inhibitor, Enavogliflozin, and a control group (placebo group). This study aims to investigate whether SGLT2 inhibitors can prevent the recurrence of AF after the procedure. Background: AF is the most common arrhythmia requiring treatment, with its prevalence increasing with age. In the US, AF affected 5.2 million people in 2010 and is projected to reach 12.1 million by 2030. In South Korea, prevalence rose from 0.73% in 2006 to 1.53% in 2015. Early-stage AF patients benefit more from rhythm control therapy than from heart rate control alone, as shown by the 2020 EAST-AFNET-4 trial, which reported a 21% reduction in adverse cardiovascular events. Catheter ablation for rhythm control significantly reduces AF recurrence compared to antiarrhythmic drugs, leading to more patients undergoing this procedure. AF and heart failure often coexist, forming a vicious cycle that exacerbates both conditions and leads to poorer outcomes. They share common risk factors like hypertension, diabetes, ischemic heart disease, and valvular disease. Heart failure increases left atrial filling pressure and alters intracellular calcium levels, raising AF risk. Further research is needed on their pathophysiological link. SGLT2 inhibitors reduce glucose reabsorption in the kidneys to control hyperglycemia in diabetics and have been shown in large studies (DAPA-HF, EMPEROR-Reduced) to significantly reduce heart failure worsening and cardiovascular mortality, regardless of diabetes status. These benefits were seen in both HFrEF and HFpEF. In the DAPA-HF trial, 55% of participants were non-diabetic, and reductions in heart failure worsening or cardiovascular death were similar between those with and without diabetes (25% vs. 27%). Adverse events, including volume depletion and renal function decline, were not significantly different between diabetic and non-diabetic patients, and no hypoglycemia or ketoacidosis occurred in non-diabetic patients. Recent studies show SGLT2 inhibitors reduce AF incidence and benefit heart failure. A sub-analysis of the DECLARE-TIMI 58 trial reported a 19% reduction in AF risk among diabetic patients with SGLT2 inhibitors. Meta-analyses by Okunrintemi and Zheng showed an 18% reduction in AF risk irrespective of diabetes status. Interest is growing in the relationship between SGLT2 inhibitors and AF recurrence post-catheter ablation. Luo et al. reported a nearly 39% reduction in AF recurrence post-ablation with dapagliflozin in diabetic patients. Kishima et al. found a 49% reduction in AF recurrence post-ablation with SGLT2 inhibitors versus DPP-IV inhibitors in a small prospective randomized study. However, most studies were retrospective, sub-analyses, or small-scale studies limited to diabetics. Prospective randomized studies involving AF patients regardless of diabetes status are urgently needed for validation.