Targeting NAD+ Metabolism to Modulate Autoimmunity and Inflammation.

NAD+ biology is involved in controlling redox balance, functioning as a coenzyme in numerous enzymatic reactions, and is a cofactor for Sirtuin enzymes and a substrate for multiple regulatory enzyme reactions within and outside the cell. At the same time, NAD+ levels are diminished with aging and are consumed during the development of inflammatory and autoimmune diseases linked to aberrant immune activation. Direct NAD+ augmentation via the NAD+ salvage and Priess-Handler pathways is being investigated as a putative therapeutic intervention to improve the healthspan in inflammation-linked diseases. In this review, we survey NAD+ biology and its pivotal roles in the regulation of immunity and inflammation. Furthermore, we discuss emerging studies evaluate NAD+ boosting in murine models and in human diseases, and we highlight areas of research that remain unresolved in understanding the mechanisms of action of these nutritional supplementation strategies.

Propionate functions as a feeding state-dependent regulatory metabolite to counter proinflammatory signaling linked to nutrient load and obesity.

Generally, fasting and refeeding confer anti- and proinflammatory effects, respectively. In humans, these caloric-load interventions function, in part, via regulation of CD4+ T cell biology. However, mechanisms orchestrating this regulation remain incomplete. We employed integrative bioinformatics of RNA sequencing and high-performance liquid chromatography-mass spectrometry data to measure serum metabolites and gene expression of peripheral blood mononuclear cells isolated from fasting and refeeding in volunteers to identify nutrient-load metabolite-driven immunoregulation. Propionate, a short chain fatty acid (SCFA), and the SCFA-sensing G protein-coupled receptor 43 (ffar2) were coordinately and inversely regulated by fasting and refeeding. Propionate and free fatty acid receptor agonists decreased interferon-γ and interleukin-17 and significantly blunted histone deacetylase activity in CD4+ T cells. Furthermore, propionate blunted nuclear factor κB activity and diminished interleukin-6 release. In parallel, propionate reduced phosphorylation of canonical T helper 1 (TH1) and TH17 regulators, STAT1 and STAT3, respectively. Conversely, knockdown of free fatty acid receptors significantly attenuated the anti-inflammatory role of propionate. Interestingly, propionate recapitulated the blunting of CD4+ TH cell activation in primary cells from obese individuals, extending the role of this metabolite to a disease associated with low-grade inflammation. Together, these data identify a nutrient-load responsive SCFA-G protein-coupled receptor linked pathway to regulate CD4+ TH cell immune responsiveness.

Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting.

Elevated interleukin (IL)-1ß levels, NLRP3 inflammasome activity, and systemic inflammation are hallmarks of chronic metabolic inflammatory syndromes, but the mechanistic basis for this is unclear. Here, we show that levels of plasma IL-1ß are lower in fasting compared to fed subjects, while the lipid arachidonic acid (AA) is elevated. Lipid profiling of NLRP3-stimulated mouse macrophages shows enhanced AA production and an NLRP3-dependent eicosanoid signature. Inhibition of cyclooxygenase by nonsteroidal anti-inflammatory drugs decreases eicosanoid, but not AA, production. It also reduces both IL-1ß and IL-18 production in response to NLRP3 activation. AA inhibits NLRP3 inflammasome activity in human and mouse macrophages. Mechanistically, AA inhibits phospholipase C activity to reduce JNK1 stimulation and hence NLRP3 activity. These data show that AA is an important physiological regulator of the NLRP3 inflammasome and explains why fasting reduces systemic inflammation and also suggests a mechanism to explain how nonsteroidal anti-inflammatory drugs work.

Serial Changes of Fatty Degeneration and Clinical Outcomes after Repair of Medium-Sized Rotator Cuff Tears

Background@#This study was designed to longitudinally analyze quantitative intramuscular and perimuscular fat and evaluate clinical outcomes according to healing degree after rotator cuff repair. @*Methods@#From June 2013 through October 2018, patients who had undergone repair due to medium-sized rotator cuff tears and serial chest computed tomography (CT) preoperatively and at early (6–12 months) and late (at least 3 years) postoperative followups were included. Supraspinatus (SST) intramuscular fat fraction ratio (IFFR) and perimuscular fat fraction ratio (PFFR) were calculated using chest CT. The rotator cuff integrity was categorized as healed, smaller retear (SRT), and larger retear (LRT) by comparing the preoperative tear size and retear size in shoulder CT arthrography at postoperative follow-ups. Clinical outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score, the University of California at Los Angeles (UCLA) shoulder rating scale, and the Constant score preoperatively and at early and late postoperative follow-ups. @*Results@#In the LRT group, compared with the preoperative values, there were increases in the SST IFFR and PFFR at the early (p = 0.002 and p = 0.006, respectively) and late (p < 0.001 and p < 0.001, respectively) postoperative time points. Late postoperative clinical scores (UCLA and Constant scores) were not improved compared to preoperative scores (p = 0.156 and p = 0.094, respectively). In the SRT group, there was no difference in the mean SST IFFR and PFFR between preoperative and early postoperative time points (p = 0.766 and p = 0.180, respectively), but the late postoperative values were higher than preoperative values (p = 0.009 and p = 0.049, respectively). Late postoperative clinical scores (ASES, UCLA, and Constant scores) in the SRT group improved compared to preoperative time (p < 0.001, p < 0.001, and p = 0.016, respectively). In the healed group, compared with the preoperative values, there was no difference in the mean SST IFFR and PFFR at postoperative time points; however, the late postoperative clinical scores (ASES, UCLA, and Constant scores) were improved (all p < 0.001). @*Conclusions@#In the SRT group, IFFR and PFFR progressed in the late postoperative period and clinical scores improved over time.However, in the LRT group, IFFR and PFFR progressed in the early and late postoperative periods and clinical scores did not improve at the late postoperative follow-up.

Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part III. Management of Advanced Differentiated Thyroid Cancers - Chapter 1-2. Locally Recurred/Persistent Thyroid Cancer Management Strategies 2024

These guidelines aim to establish the standard practice for diagnosing and treating patients with differentiated thyroid cancer (DTC). Based on the Korean Thyroid Association (KTA) Guidelines on DTC management, the “Treatment of Advanced DTC” section was revised in 2024 and has been provided through this chapter. Especially, this chapter covers surgical and nonsurgical treatments for the local (previous surgery site) or regional (cervical lymph node metastasis) recurrences. After drafting the guidelines, it was finalized by collecting opinions from KTA members and related societies. Surgical resection is the preferred treatment for local or regional recurrence of advanced DTC. If surgical resection is not possible, nonsurgical resection treatment under ultrasonography guidance may be considered as an alternative treatment for local or regional recurrence of DTC. Furthermore, if residual lesions are suspected even after surgical resection or respiratory-digestive organ invasion, additional radioactive iodine and external radiation treatments are considered.

Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part V. Pediatric Differentiated Thyroid Cancer 2024

Pediatric differentiated thyroid cancers (DTCs), mostly papillary thyroid cancer (PTC, 80-90%), are diagnosed at more advanced stages with larger tumor sizes and higher rates of locoregional and/or lung metastasis. Despite the higher recurrence rates of pediatric cancers than of adult thyroid cancers, pediatric patients demonstrate a lower mortality rate and more favorable prognosis. Considering the more advanced stage at diagnosis in pediatric patients, preoperative evaluation is crucial to determine the extent of surgery required. Furthermore, if hereditary tumor syndrome is suspected, genetic testing is required. Recommendations for pediatric DTCs focus on the surgical principles, radioiodine therapy according to the postoperative risk level, treatment and follow-up of recurrent or persistent diseases, and treatment of patients with radioiodine-refractory PTCs on the basis of genetic drivers that are unique to pediatric patients.

Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Overview and Summary 2024

Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part I. Initial Management of Differentiated Thyroid Cancers - Chapter 2. Surgical Management of Thyroid Cancer 2024

The primary objective of initial treatment for thyroid cancer is minimizing treatment-related side effects and unnecessary interventions while improving patients’ overall and disease-specific survival rates, reducing the risk of disease persistence or recurrence, and conducting accurate staging and recurrence risk analysis. Appropriate surgical treatment is the most important requirement for this purpose, and additional treatments including radioactive iodine therapy and thyroid-stimulating hormone suppression therapy are performed depending on the patients’ staging and recurrence risk. Diagnostic surgery may be considered when repeated pathologic tests yield nondiagnostic results (Bethesda category 1) or atypia of unknown significance (Bethesda category 3), depending on clinical risk factors, nodule size, ultrasound findings, and patient preference. If a follicular neoplasm (Bethesda category 4) is diagnosed pathologically, surgery is the preferred option. For suspicious papillary carcinoma (suspicious for malignancy, Bethesda category 5), surgery is considered similar to a diagnosis of malignancy (Bethesda category 6). As for the extent of surgery, if the cancer is ≤1 cm in size and clinically free of extrathyroidal extension (ETE) (cT1a), without evidence of cervical lymph node (LN) metastasis (cN0), and without obvious reason to resect the contralateral lobe, a lobectomy can be performed. If the cancer is 1-2 cm in size, clinically free of ETE (cT1b), and without evidence of cervical LN metastasis (cN0), lobectomy is the preferred option. For patients with clinically evident ETE to major organs (cT4) or with cervical LN metastasis (cN1) or distant metastasis (M1), regardless of the cancer size, total thyroidectomy and complete cancer removal should be performed at the time of initial surgery. Active surveillance may be considered for adult patients diagnosed with low-risk thyroid papillary microcarcinoma. Endoscopic and robotic thyroidectomy may be performed for low-risk differentiated thyroid cancer when indicated, based on patient preference.

Association Between Individual Air Pollution (PM 10 , PM2.5) Exposure and Adverse Pregnancy Outcomes in Korea: A Multicenter Prospective Cohort, Air Pollution on Pregnancy Outcome (APPO) Study

Background@#Prenatal exposure to ambient air pollution is linked to a higher risk of unfavorable pregnancy outcomes. However, the association between pregnancy complications and exposure to indoor air pollution remains unclear. The Air Pollution on Pregnancy Outcomes research is a hospital-based prospective cohort research created to look into the effects of aerodynamically exposed particulate matter (PM) 10 and PM 2.5 on pregnancy outcomes. @*Methods@#This prospective multicenter observational cohort study was conducted from January 2021 to June 2023. A total of 662 women with singleton pregnancies enrolled in this study. An AirguardK ® air sensor was installed inside the homes of the participants to measure the individual PM 10 and PM 2.5 levels in the living environment. The time–activity patterns and PM 100 and PM 2.5 , determined as concentrations from the time-weighted average model, were applied to determine the anticipated exposure levels to air pollution of each pregnant woman. The relationship between air pollution exposure and pregnancy outcomes was assessed using logistic and linear regression analyses. @*Results@#Exposure to elevated levels of PM 10 throughout the first, second, and third trimesters as well as throughout pregnancy was strongly correlated with the risk of pregnancy problems according to multiple logistic regression models adjusted for variables. Except for in the third trimester of pregnancy, women exposed to high levels of PM 2.5 had a high risk of pregnancy complications. During the second trimester and entire pregnancy, the risk of preterm birth (PTB) increased by 24% and 27%, respectively, for each 10 μg/m 3 increase in PM 10. Exposure to high PM 10 levels during the second trimester increased the risk of gestational diabetes mellitus (GDM) by 30%. The risk of GDM increased by 15% for each 5 μg/m 3 increase in PM2.5 during the second trimester and overall pregnancy, respectively. Exposure to high PM 10 and PM 2.5 during the first trimester of pregnancy increased the risk of delivering small for gestational age (SGA) infants by 96% and 26%, respectively. @*Conclusion@#Exposure to high concentrations of PM 10 and PM 2.5 is strongly correlated with the risk of adverse pregnancy outcomes. Exposure to high levels of PM10 and PM2.5 during the second trimester and entire pregnancy, respectively, significantly increased the risk of PTB and GDM. Exposure to high levels of PM 10 and PM2.5 during the first trimester of pregnancy considerably increased the risk of having SGA infants. Our findings highlight the need to measure individual particulate levels during pregnancy and the importance of managing air quality in residential environment.

Comparison of the Clinical Outcomes Between Early and Delayed Transplantation After SARS-CoV-2Infection

Our study analyzed 95 solid organ transplant (SOT) and 78 hematopoietic stem cell transplant (HSCT) recipients with prior coronavirus disease 2019 (COVID-19). Patients who underwent transplantation within 30 days of COVID-19 infection comprised the early group, and those who underwent transplantation post-30 days of COVID-19 infection comprised the delayed group. In the early transplantation group, no patient, whether undergoing SOT and HSCT, experienced COVID-19-associated complications. In the delayed transplantation group, one patient each from SOT and HSCT experienced COVID-19-associated complications. Additionally, among early SOT and HSCT recipients, two and six patients underwent transplantation within seven days of COVID-19 diagnosis, respectively. However, no significant differences were observed in the clinical outcomes of these patients compared to those in other patients. Early transplantation following severe acute respiratory syndrome coronavirus 2 infection can be performed without increased risk of COVID-19-associated complications. Therefore, transplantation needs not be delayed by COVID-19 infection.

Effects of Transport to Trauma Centers on Survival Outcomes Among Severe Trauma Patients in Korea: Nationwide Age-Stratified Analysis

Background@#Previous studies showed that the prognosis for severe trauma patients is better after transport to trauma centers compared to non-trauma centers. However, the benefit from transport to trauma centers may differ according to age group. The aim of this study was to compare the effects of transport to trauma centers on survival outcomes in different age groups among severe trauma patients in Korea. @*Methods@#Cross-sectional study using Korean national emergency medical service (EMS) based severe trauma registry in 2018–2019 was conducted. EMS-treated trauma patients whose injury severity score was above or equal to 16, and who were not out-of-hospital cardiac arrest or death on arrival were included. Patients were classified into 3 groups:pediatrics (age 65). The primary outcome was in-hospital mortality. Multivariable logistic regression analysis was conducted to evaluate the effect of trauma center transport on outcome after adjusting of age, sex, comorbidity, mechanism of injury, Revised Trauma Score, and Injury Severity Score. All analysis was stratified according to the age group, and subgroup analysis for traumatic brain injury was also conducted. @*Results@#Overall, total of 10,511 patients were included in the study, and the number of patients in each age group were 488 in pediatrics, 6,812 in working age, and 3,211 in elderly, respectively. The adjusted odds ratio (95% confidence interval [CI]) of trauma center transport on in-hospital mortality from were 0.76 (95% CI, 0.43–1.32) in pediatrics, 0.78 (95% CI, 0.68–0.90) in working age, 0.71(95% CI, 0.60–0.85) in elderly, respectively. In subgroup analysis of traumatic brain injury, the benefit from trauma center transport was observed only in elderly group. @*Conclusion@#We found out trauma centers showed better clinical outcomes for adult and elderly groups, excluding the pediatric group than non-trauma centers. Further research is warranted to evaluate and develop the response system for pediatric severe trauma patients in Korea.

Retrospective Multicenter Analysis of Prognostic Risk Factors for One Year Recurrence in Patient With Renal Cell Carcinoma After Partial or Radical Nephrectomy: Results of Korean Renal Cancer Study Group (KRoCS) Database

Background@#We sought to identify prognostic risk factors for one year recurrence in patient with renal cell carcinoma (RCC) after partial or radical nephrectomy. @*Methods@#We performed a retrospective study of 1,269 patients with RCC after partial or radical nephrectomy and diagnosed recurrence using Korean Renal Cancer Study Group (KRoCS) database between January 1991 and March 2017. Recurrence-free survival (RFS), and overall survival (OS) were calculated using the Kaplan–Meier method and multivariate Cox regression analysis were performed to evaluate independent prognostic factors for recurrence. @*Results@#The median patient age was 56 years and median follow-up period was 67 months.Multivariable analysis demonstrated BMI greater than or equal to 23 and less than 30 (vs. BMI less than 23, hazard ratio [HR]: 0.707, P = 0.020) reduced recurrence one year postoperatively. Eastern Cooperative Oncology Group performance status (ECOG PS) greater than or equal to 1 (vs. ECOG PS 0, HR: 1.548, P = 0.007), high pathological T stage (pT2 vs.pT1, HR: 2.622, P < 0.001; pT3 vs. pT1, HR: 4.256, P < 0.001; pT4 vs. pT1, HR: 4.558, P < 0.001), and tumor necrosis (vs. no tumor necrosis, HR: 2.822, P < 0.001) were independent predictive factors for early recurrence within one year in patients with RCC. Statistically significant differences on RFS and OS were found among pathological T stages (pT2 vs. pT1; pT3 vs. pT1; pT4 vs. pT1, all P < 0.001). @*Conclusion@#This large multicenter study demonstrated ECOG PS greater than or equal to 1, high pathological T stage, tumor necrosis and BMI less than 23 were significant prognostic risk factors of early recurrence within one year in patients with RCC who underwent nephrectomy.

Evolution of blaKPC Under the Pressure of Carbapenems and Ceftazidime/ Avibactam in a Patient With Persistent Bacteremia Caused by Klebsiella pneumoniae

A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/ avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance.Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of blaKPC variants.

Late Parasitological Failure and Subsequent Isolated Gametocytemia of Uncomplicated Plasmodium falciparum Malaria in a Returned Traveler From Ghana, 2023

Herein, we report a case of uncomplicated falciparum malaria with late parasitological failure in a 45-year-old businessman returning from Ghana. The patient visited the emergency department with high fever, headache, and dizziness. He traveled without antimalarial chemoprophylaxis. Laboratory tests led to the diagnosis of uncomplicated falciparum malaria with an initial density of 37,669 parasites per μL of blood (p/μL). The patient was treated with intravenous artesunate followed by atovaquone/proguanil. He was discharged with improved condition and decreased parasite density of 887 p/μL. However, at follow-up, parasite density increased to 7,630 p/μL despite the absence of any symptoms. Suspecting treatment failure, the patient was administered intravenous artesunate and doxycycline for seven days and then artemether/lumefantrine for three days. Blood smear was negative for asexual parasitemia after re-treatment but positive for gametocytemia until day 101 from the initial diagnosis. Overall, this case highlights the risk of late parasitological failure in patients with imported uncomplicated falciparum malaria.

Effect of a new handover system for 119 transfer patients in a single emergency medical center

Objective@#This study evaluated the efficacy and effectiveness of a new patient handover system developed for better handover in a metropolitan emergency department (ED). @*Methods@#A retrospective observational study was designed to evaluate the appropriateness and satisfaction level of the new ED handover system. The participants were pre-hospital emergency medical service (EMS) providers with patient transport experience before and after the pilot of the new handover system. @*Results@#A questionnaire was completed by 37 pre-hospital EMS providers who transported patients to the emergency department. Based on the results, pre-hospital EMS providers felt an increased level of kindness from the ED healthcare professionals during patient handover (P<0.001), from 3.19±1.05 points before the introduction of the system to 3.97±0.96 points after its introduction, and the activeness of ED healthcare professionals also increased, from 3.35±1.03 to 4.14±0.86 points (P<0.001). The sufficiency of contents of patient handover information to explain a patient’s condition increased from 3.59±0.76 to 4.08±0.72 points (P<0.003). The score for overall satisfaction felt by the EMS providers during patient handover increased from 3.46±0.96 to 3.76±0.86 points, which was not statistically significant (P=0.020). @*Conclusion@#Our findings suggest that the introduction of a new patient handover system between EMS providers and the ED staff is effective for both pre-hospital EMS providers and ED staff.

Beyond the surface: unraveling global health curriculum insights through interviews of learners and educators using the CIPP model / 한국의학교육

Purpose@#Our study aimed to delve beyond a surface-level understanding and explore the various dimensions of the global health curriculum from the perspective of both learners and educators using the Context, Input, Process, and Product (CIPP) model. @*Methods@#From 2020 to 2021, interviews were conducted with a total of 10 individuals, including five students who had taken at least one elective course and at least one elective research course, three teaching assistants (TA), and two faculty members who had taken more than four global health courses in multiple phases in the global health curriculum. Semi-structured interview questions based on the CIPP model were used and qualitative data were analyzed through content analysis. @*Results@#The study identified 12 sub-themes. Students held idealized views of global health careers and sought to bridge the gap through global health classes. They desired early exposure to global health courses, emphasizing both pre-medical and clinical phases. Challenges in adjusting course difficulty and recruiting faculty were identified, along with a preference for interactive teaching methods and offline discussions. The curriculum promoted reflection on medicine’s essence, expanded career perspectives, and emphasized competencies like altruism, communication skills, and crisis management in the evolving global health landscape. @*Conclusion@#This study showed that a comprehensive approach is possible from the perspective of learners and educators by identifying strengths, weaknesses, and the value of the curriculum’s goals, plans, implementations, and results through the CIPP model. For optimal curriculum design, a sequential approach from basic to advanced courses is essential, promoting hands-on global health experiences for students.

Implant-supported fixed prosthesis restoration of fully edentulous patient using computer-guided implant surgery and immediate loading: A case report / 대한치과보철학회지

In a edentulous patient, various methods can be employed for prosthetic treatment using implants, such as implant-supported fixed prostheses, overdentures, hybrid prostheses, and implant assisted removable partial denture. In this case, in a patient with moderate to severe chronic periodontitis requiring full arch extractions, implants were strategically placed using computer-guided surgery. In the maxilla, due to inadequate bone quality and quantity leading to insufficient initial stability, delayed loading was implemented, and interim prosthesis was used during the osseointegration period. In the mandible, stable initial stability was achieved, allowing for immediate loading to reduce patient discomfort.Primary stability is considered the most crucial factor for obtaining immediate loading, so a thorough clinical and radiological evaluation of the remaining alveolar bone quantity and quality must be conducted before surgery.

Time to presentation and mortality outcomes among patients with diabetes and acute myocardial infarction

Background/Aims@#Due to limited real-world evidence on the association between time to presentation (T2P) and outcomes following acute myocardial infarction and diabetes (AMI-DM), we investigated the characteristics of patients with AMI-DM and their outcomes based on their T2P. @*Methods@#4,455 patients with AMI-DM from a Korean nationwide observational cohort (2011–2015) were divided into early and late presenters according to symptom-to-door time. The effects of T2P on three-year all-cause mortality were estimated using inverse probability of treatment weighting (IPTW) and survival analysis. @*Results@#The incidence of all-cause mortality was consistently higher in late presenters than in early presenters (11.4 vs. 17.2%; p < 0.001). In the IPTW-adjusted dataset, the incidence of all-cause mortality was numerically higher in late presenters than in early presenters (9.1 vs. 12.4%; p = 0.072). In the survival analysis, the cumulative incidence of all-cause mortality was significantly higher in late presenters than in early presenters before and after IPTW. In the subgroup with ST-elevation myocardial infarction, late presenters had a higher incidence of cardiac death than early presenters before (4.8 vs. 10.5%; p < 0.001) and after IPTW (4.2 vs. 9.7%; p = 0.034). In the initial glycated hemoglobin (HbA1c)-stratified analysis, these effects were attenuated in patients with HbA1c ≥ 9.0% before (adjusted hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 0.80-2.64) and after IPTW (adjusted HR: 0.82, 95% CI: 0.40-1.67). @*Conclusions@#Late presentation was associated with higher mortality in patients with AMI-DM; therefore, multifaceted and systematic interventions are needed to decrease pre-hospital delays.

Model for end-stage liver disease-3.0 vs. model for end-stage liver disease-sodium: mortality prediction in Korea

Background/Aims@#The model for end-stage liver disease (MELD) serves as an indicator for short-term mortality among patients diagnosed with liver cirrhosis (LC) and is used to prioritize patients for liver transplantation. In 2021, the updated version of MELD, MELD-3.0, was introduced to improve the accuracy of the mortality prediction of MELD. Therefore, this study aimed to compare the efficacy of MELD 3.0 and MELD-Na in predicting mortality among Korean patients with LC. @*Methods@#A retrospective review was conducted using the medical records of patients diagnosed with LC who were admitted to Konkuk University Hospital From 2011 to 2021. The study calculated the predictive values of MELD-Na and MELD-3.0 for 3- and 6-months mortality using the area under the receiver operating curve (AUROC) and compared the results using the DeLong test. @*Results@#Of the 3,034 patients enrolled in the study, 339 (11.2%) died within 3 months and 421 (14.4%) died within 6 months. The AUROCs values for predicting 3 months mortality were 0.846 for MELD-Na and 0.851 for MELD-3.0. The corresponding AUROC values for predicting 6 months mortality were 0.843 for MELD-Na and 0.848 for MELD-3.0. MELD-3.0 exhibited better discrimination ability than MELD-Na for both 3 (p = 0.03) and 6 months mortality (p = 0.01). @*Conclusions@#Our study found a significant difference between the performance of MELD-3.0 and MELD-Na in Korean patients with LC.

Preliminary Investigation on Efficacy and Safety of Substance P-Coated Stent for Promoting Re-Endothelialization: A Porcine Coronary Artery Restenosis Model

BACKGROUND@#Current polymer-based drug-eluting stents (DESs) have fundamental issues about inflammation and delayed re-endothelializaton of the vessel wall. Substance-P (SP), which plays an important role in inflammation and endothelial cells, has not yet been applied to coronary stents. Therefore, this study compares poly lactic-co-glycolic acid (PLGA)-based everolimus-eluting stents (PLGA-EESs) versus 2-methacryloyloxyethyl phosphorylcholine (MPC)-based SP-eluting stents (MPC-SPs) in in-vitro and in-vivo models. @*METHODS@#The morphology of the stent surface and peptide/drug release kinetics from stents were evaluated. The invitro proliferative effect of SP released from MPC-SP is evaluated using human umbilical vein endothelial cell. Finally, the safety and efficacy of the stent are evaluated after inserting it into a pig’s coronary artery. @*RESULTS@#Similar to PLGA-EES, MPC-SP had a uniform surface morphology with very thin coating layer thickness (2.074 lm). MPC-SP showed sustained drug release of SP for over 2 weeks. Endothelial cell proliferation was significantly increased in groups treated with SP (n = 3) compared with the control (n = 3) and those with everolimus (n = 3) (SP:118.9 ± 7.61% vs. everolimus: 64.3 ± 12.37% vs. the control: 100 ± 6.64%, p < 0.05). In the animal study, the percent stenosis was higher in MPC-SP group (n = 7) compared to PLGA-EES group (n = 7) (MPC-SP: 28.6 ± 10.7% vs. PLGAEES: 16.7 ± 6.3%, p < 0.05). MPC-SP group showed, however, lower inflammation (MPC-SP: 0.3 ± 0.26 vs. PLGAEES: 1.2 ± 0.48, p < 0.05) and fibrin deposition (MPC-SP: 1.0 ± 0.73 vs. PLGA-EES: 1.5 ± 0.59, p < 0.05) around the stent strut. MPC-SP showed more increased expression of cluster of differentiation 31, suggesting enhanced reendothelialization. @*CONCLUSION@#Compared to PLGA-EES, MPC-SP demonstrated more decreased inflammation of the vascular wall and enhanced re-endothelialization and stent coverage. Hence, MPC-SP has the potential therapeutic benefits for the treatment of coronary artery disease by solving limitations of currently available DESs.