Disease progression modeling with temporal realignment: An emerging approach to deepen knowledge on chronic diseases.

The recent development of the first disease-modifying drug for Alzheimer's disease represents a major advancement in dementia treatment. Behind this breakthrough is a quarter century of research efforts to understand the disease not by a particular symptom at a given moment, but by long-term sequential changes in multiple biomarkers. Disease progression modeling with temporal realignment (DPM-TR) is an emerging computational approach proposed with this biomarker-based disease concept. By integrating short-term clinical observations of multiple disease biomarkers in a data-driven manner, DPM-TR provides a way to understand the progression of chronic diseases over decades and predict individual disease stages more accurately. DPM-TR has been developed primarily in the area of neurodegenerative diseases but has recently been extended to non-neurodegenerative diseases, including chronic obstructive pulmonary, autoimmune, and ophthalmologic diseases. This review focuses on opportunities for DPM-TR in clinical practice and drug development and discusses its current status and challenges.

Risk factors for infliximab-induced infusion reactions based on a retrospective study of medical information.

OBJECTIVE: Infliximab is indicated for a wide range of diseases, and infusion reactions (IRs) have been reported after infliximab administration in 17.6% of patients in clinical practice. This study aimed to identify the risk factors for IRs before the administration of infliximab based on available patient information. MATERIALS AND METHODS: We retrospectively analyzed patients treated with infliximab. Data were compared between patients with and without IRs immediately before initiation of infliximab. RESULTS: Elevated C-reactive protein (CRP) (odds ratio (OR), 2.150; 95% confidence interval (CI), 1.329 - 3.477; p = 0.002) before infliximab administration was a significant risk factor for developing an IR. CONCLUSION: Patients with elevated CRP levels before therapy initiation may require more careful monitoring after infliximab administration.

A case of spontaneous coronary artery dissection that later turned out to be Takayasu arteritis.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS), which typically occurs in women at low risk of atherosclerosis. We herein report a case of SCAD in a 57-year-old man who later developed Takayasu arteritis. The patient presented to our hospital complaining of chest pain and was diagnosed with unstable angina. Emergent coronary angiography was performed, and optical coherence tomography revealed that ACS was caused by SCAD. The patient was treated medically without further ballooning or stenting. Because there was a bilateral difference in blood pressure, the systemic artery was screened by contrast-enhanced computed tomography, which showed left subclavian artery occlusion, proximal stenosis of the superior mesenteric artery, right common iliac artery dissection, and left external iliac artery dissection. Based on these results and 18F-fluorodeoxyglucose positron emission tomography findings, we diagnosed Takayasu arteritis. Prednisolone and tocilizumab were selected for medical treatment, and the patient was in a good condition at one year after the diagnosis. Takayasu arteritis can cause dissection of various arteries and should be suspected when atypical SCAD or multiple dissections are present. Early initiation of immunosuppressive therapy can control disease activity. Learning objective: Spontaneous coronary artery dissection (SCAD) is an important cause of acute coronary syndrome. In this case, we experienced a case of SCAD which turned out to be the first symptom of Takayasu arteritis. Immunosuppressive therapy was effective for both coronary lesion and systemic vasculitis. Not only fibromuscular dysplasia, but also various types of vasculitis should therefore be considered in the differential diagnosis when encountering atypical SCAD cases.

Shock absorption and dispersion capability of a novel five-layer mouthguard sheet material.

There is a growing need for a mouthguard sheet material with higher shock absorption and dispersion capacity than those obtained by conventional materials. A five-layer mouthguard sheet material was previously developed using laminated ethylene vinyl acetate and polyolefin copolymer resin. In this study, the shock absorption capacity and dispersion capability of the new sheet material were investigated and compared with those of other materials. Impact testing for the new sheet material showed that the force required to displace the sheet by 1 mm was significantly higher at all thicknesses (p<0.001), whereas the puncture energy and displacement were significantly lower than those for ethylene vinyl acetate (p<0.05). The five-layer mouthguard sheet material successfully absorbed and resisted shock. Therefore, the sheet material potentially increases resistance to applied deformation in teeth and alveolar bone and maintains structure. The five-layer sheet material could expand the range of mouthguard products and help prevent oral trauma.

Approach using the bath preparation containing rice extract for severe pruritus in a patient receiving hemodialysis: A case report.

Severe pruritus in a hemodialysis patient who had difficulty applying topical medication markedly reduced with the use of bath preparation containing rice extract. The bath preparation could be effective and an option for treating pruritus.

Coagulopathy Induced by Antibiotics Usage and Bowel Obstruction With Colon Cancer: Report of a Rare Case.

This case report presents a rare occurrence of coagulopathy induced by antibiotics in a woman in her 90s with chronic bowel obstruction and massive colon cancer. The patient developed vitamin K deficiency-related coagulopathy following antibiotic administration, resulting in bleeding complications. Despite initial consideration of disseminated intravascular coagulation, further investigations revealed antibiotic-induced vitamin K deficiency. Prompt discontinuation of antibiotics and IV vitamin K2 administration led to the resolution of coagulopathy. The case emphasizes the importance of cautious antibiotic use in patients with chronic bowel obstruction and prolonged fasting. The protein induced by vitamin K absence-II (PIVKA-II) proved valuable in diagnosing vitamin K deficiency. The learning points include the potential for coagulopathy with antibiotics in prolonged bowel obstruction and the utility of PIVKA-II in assessing vitamin K deficiency. Healthcare providers should exercise caution when administering antibiotics in similar clinical scenarios.

Combination of rRT-PCR and Clinical Features to Predict Coronavirus Disease 2019 for Nosocomial Infection Control.

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), immediately became a pandemic. Therefore, nosocomial infection control is necessary to screen for patients with possible COVID-19. Objective: This study aimed to investigate commonly measured clinical variables to predict COVID-19. Methods: This cross-sectional study enrolled 1087 patients in the isolation ward of a university hospital. Conferences were organized to differentiate COVID-19 from non-COVID-19 cases, and multiple nucleic acid tests were mandatory when COVID-19 could not be excluded. Multivariate logistic regression models were employed to determine the clinical factors associated with COVID-19 at the time of hospitalization. Results: Overall, 352 (32.4%) patients were diagnosed with COVID-19. The majority of the non-COVID-19 cases were predominantly caused by bacterial infections. Multivariate analysis indicated that COVID-19 was significantly associated with age, sex, body mass index, lactate dehydrogenase, C-reactive protein, and malignancy. Conclusion: Some clinical factors are useful to predict patients with COVID-19 among those with symptoms similar to COVID-19. This study suggests that at least two real-time reverse-transcription polymerase chain reactions of SARS-CoV-2 are recommended to exclude COVID-19.

Mechanisms of Very Late Stent Thrombosis in Japanese Patients as Assessed by Optical Coherence Tomography.

BACKGROUND: Although very late stent thrombosis (VLST) remains an important concern, the underlying etiology and clinical characteristics are not fully elucidated in Japanese patients who undergo intravascular imaging-guided percutaneous coronary intervention (PCI) regularly. METHODS: We identified 50 VLST lesions (bare-metal stent [BMS] [n = 16], first-generation drug-eluting stent [DES] [n = 14] and newer-generation DES [n = 20]) in patients managed in our institutes. The underlying mechanism of VLST was assessed by optical coherence tomography (OCT), and the major etiology of each lesion was determined. The aim of this study was to explore the mechanisms of VLST of BMSs and DESs in Japanese patients. RESULTS: The median duration since stent implantation was 10 years (range: 1-20). The most frequent etiology of VLST was neoatherosclerotic rupture (44%), followed by neointimal erosion (24%). Edge disease (10%) and evagination (10%) were similarly observed. Malapposition (8%) was deemed to be acquired late by looking at intravascular imaging from the index procedure. Uncovered struts (2%) and in-stent calcified nodule (2%) were the least frequent etiologies. Regardless of etiology, signs of neoatherosclerosis were present in most lesions (82%). Most patients received single (68%) or dual (8%) antiplatelet therapy or oral anticoagulation alone (4%), whereas a considerable proportion of patients discontinued medication (20%). Regarding the treatment strategy, drug-coated balloon was the most frequent strategy (56%), followed by implantation of newer DESs (34%). CONCLUSIONS: Various mechanisms have been identified in Japanese patients with VLST. In these patients, biological responses seemed to be more relevant than the index procedure-related factors.

An Aspirin-Free Versus Dual Antiplatelet Strategy for Coronary Stenting: STOPDAPT-3 Randomized Trial.

BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

Distinct microRNA Signature and Suppression of ZFP36L1 Define ASCL1-Positive Lung Adenocarcinoma.

Achaete-scute family bHLH transcription factor 1 (ASCL1) is a master transcription factor involved in neuroendocrine differentiation. ASCL1 is expressed in approximately 10% of lung adenocarcinomas (LUAD) and exerts tumor-promoting effects. Here, we explored miRNA profiles in ASCL1-positive LUADs and identified several miRNAs closely associated with ASCL1 expression, including miR-375, miR-95-3p/miR-95-5p, miR-124-3p, and members of the miR-17∼92 family. Similar to small cell lung cancer, Yes1 associated transcriptional regulator (YAP1), a representative miR-375 target gene, was suppressed in ASCL1-positive LUADs. ASCL1 knockdown followed by miRNA profiling in a cell culture model further revealed that ASCL1 positively regulates miR-124-3p and members of the miR-17∼92 family. Integrative transcriptomic analyses identified ZFP36 ring finger protein like 1 (ZFP36L1) as a target gene of miR-124-3p, and IHC studies demonstrated that ASCL1-positive LUADs are associated with low ZFP36L1 protein levels. Cell culture studies showed that ectopic ZFP36L1 expression inhibits cell proliferation, survival, and cell-cycle progression. Moreover, ZFP36L1 negatively regulated several genes including E2F transcription factor 1 (E2F1) and snail family transcriptional repressor 1 (SNAI1). In conclusion, our study revealed that suppression of ZFP36L1 via ASCL1-regulated miR-124-3p could modulate gene expression, providing evidence that ASCL1-mediated regulation of miRNAs shapes molecular features of ASCL1-positive LUADs. IMPLICATIONS: Our study revealed unique miRNA profiles of ASCL1-positive LUADs and identified ASCL1-regulated miRNAs with functional relevance.

Lifestyle Intervention With Smartphone App and isCGM for People at High Risk of Type 2 Diabetes: Randomized Trial.

AIMS: Although conventional interventions for people at high risk of developing type 2 diabetes are usually conducted face-to-face, such interventions are burdensome for health care providers. We developed a lifestyle intervention program combining lifestyle coaching via a smartphone application augmented by intermittently scanned continuous glucose monitoring without burdening health care providers. Its effectiveness for glycemic control and body weight reduction in people at risk of type 2 diabetes was investigated. MATERIALS AND METHODS: For this 12-week randomized unblinded trial with offline recruitment, participants with a hemoglobin A1c level of 5.6% to 6.4% or a fasting blood glucose of 110 to 125 mg/dL and body mass index (BMI) >23 kg/m2 but <40 kg/m2 were randomly assigned to the intervention group (App) and control group (C). The primary endpoint was the difference in time in range of blood glucose between 70 and 140 mg/dL (3.9-7.8 mmol/L) before and after the study period between the 2 groups. RESULTS: Among 168 patients (mean age, 48.1 years; mean BMI, 26.6 kg/m2; and male, 80.4%), 82 and 86 were assigned to the App group and C group, respectively. After 12 weeks, time in range of blood glucose at 70 to 140 mg/dL significantly improved in the App group compared with the C group (-2.6 minutes/day vs +31.5 minutes/day, P = .03). Changes in time above range did not differ, whereas time below range (blood glucose <70 mg/dL; +23.5 minutes/day vs -8.9 minutes/day, P = .02) improved in the App group. BMI (-0.26 vs -0.59, P = .017) was reduced in the App group compared with the C group. CONCLUSION: Intervention with a smartphone app and intermittently scanned continuous glucose monitoring increased glycemic control accompanied by decreased carbohydrate intake and weight loss. Further trials are needed to confirm whether these interventions can reduce incident type 2 diabetes.

Predictors of a Good Diuretic Response and Administration Methods for Carperitide in Patients With Acute Heart Failure.

PURPOSE: In Japan, carperitide has been recommended for the treatment of pulmonary congestion in patients with acute heart failure. Identifying useful indicators to support the decision to administer carperitide and the optimal timing of administration may lead to better improvement of pulmonary congestion. Therefore, we investigated the factors associated with good diuretic response to carperitide in patients with acute heart failure and the optimal timing of carperitide administration. METHODS: This retrospective cohort study investigated 293 hospitalized patients who were diagnosed with acute heart failure and treated with carperitide at the Department of Cardiology, Showa University Fujigaoka Hospital. The primary endpoint was the diuretic response to carperitide. Patients with urine output ≥100 mL/h were defined as the good diuretic response group, and those with a urine output <100 mL/h during the first 6 hours of carperitide administration were defined as the poor diuretic response group. Multivariate analysis was used to examine the predictors of good diuretic response. The relationship between the time from intravenous furosemide to carperitide administration and urine output was also investigated. FINDINGS: The patients' median age was 77 (range: 28-99) years, and 75.5% had New York Heart Association stage IV acute heart failure. The median urine output within 6 hours of carperitide administration was 104.5 (range: 6.6-1571.3) mL/h, and 118 patients (53.6%) showed a good diuretic response. Significant predictors of good diuretic response were age < 75 years [odds ratio (OR) 4.186; 95% confidence interval (CI), 2.129-8.230; P < 0.001], no prior use of loop diuretics (OR 2.155; 95% CI, 1.104-4.207; P = 0.024), blood urea nitrogen <20 mg/dL (OR 2.637; 95% CI, 1.340-5.190; P = 0.005), and white blood cell count <8.6 × 109/L (OR 3.162; 95% CI, 1.628-6.140; P = 0.001). The median urine output in the group with <2 hours between intravenous furosemide and carperitide administration was significantly higher than that in the group with an interval >6 hours [127.3; interquartile range (IQR), 77.6-216.2 mL/h vs. 66.2; IQR. 51.8-114.8 mL/h; P = 0.012). IMPLICATIONS: The 4 predictors (age, no prior use of loop diuretics, blood urea nitrogen, and white blood cell count) of good diuretic response are useful indicators to support decision-making for carperitide administration. Additionally, the administration of carperitide within 2 hours of intravenous furosemide may lead to the improvement of pulmonary congestion.

Bleeding risk factors and real-world antithrombotic therapies in elderly patients with atrial fibrillation undergoing percutaneous coronary intervention: a retrospective study.

BACKGROUND: Bleeding risk factors in elderly patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) are unclear and data on the use of antithrombotic drugs are lacking. We investigated the bleeding risk factors in elderly patients with atrial fibrillation undergoing PCI to help optimize antithrombotic therapy according to bleeding risk. We also investigated the association between the actual use of antithrombotic therapy and bleeding events. METHODS: A retrospective cohort study was conducted on 134 elderly patients with atrial fibrillation who underwent primary PCI at the Department of Cardiology, Showa University Fujigaoka Hospital. The endpoint was a bleeding event within 1-year. Bleeding risk factors were identified using multivariate analysis. The association between the number of antithrombotics and bleeding events was evaluated using the chi-squared test. RESULTS: The mean age of the patients was 76.0 ± 6.2 years. Bleeding events occurred in 41 (30.6%) patients. Age > 80 years (odds ratio [OR]: 2.54, 95% confidence interval [CI]: 1.10-5.85), multivessel disease (OR: 2.76, 95% CI: 1.22-6.23), and history of surgery (OR: 3.03, 95% CI: 1.14-8.06) were identified as bleeding risk factors. The proportion of patients receiving triple therapy was significantly higher in the bleeding group compared to the non-bleeding group (70.7% vs. 27.5%, p < 0.001). CONCLUSIONS: Age > 80, multivessel disease, and history of surgery were found to be risk factors for bleeding in elderly patients with atrial fibrillation undergoing PCI. In addition, dual therapy after PCI in elderly patients at high risk of bleeding should be considered to avoid bleeding events.

Elevation of tacrolimus concentration after administration of methotrexate for treatment of graft-versus-host disease in pediatric patients received allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Methotrexate (MTX) is used to treat graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, a case was encountered in which the blood concentration of tacrolimus (TCR) at steady state increased after intravenous MTX administration for GVHD treatment (therapeutic IV-MTX administration). Therefore, this study aimed to investigate the effect of therapeutic IV-MTX administration on the pharmacokinetics of TCR. METHODS: This single-center, retrospective, observational study included patients who underwent allo-HSCT and received therapeutic IV-MTX administration during immunosuppressive therapy with continuous intravenous infusion (CIV) of TCR from April 2004 to December 2021. Here, each therapeutic IV-MTX administration was defined as a case and independently subjected to subsequent analyses. The blood concentration of TCR at steady state (Css), ratio of Css to daily TCR dose (C/D), and clinical laboratory data were compared before and after therapeutic IV-MTX administration. In addition, dose changes in the TCR after therapeutic IV-MTX administration were evaluated. RESULTS: Ten patients (23 cases) were included in this study. The C/D value significantly increased after therapeutic IV-MTX administration (median: 697 vs. 771 (ng/mL)/(mg/kg), 1.16-fold increase, P < 0.05), indicating a reduction in the apparent clearance of TCR. Along with the increase in C/D, significant increases were observed in aspartate transaminase level (median: 51.0 vs. 92.9 U/L, P < 0.01) and alanine aminotransferase level (median: 74.5 vs. 99.4 U/L, P < 0.01) indicating that liver injury after therapeutic IV-MTX administration contributes to the observed C/D increase. In addition, the daily dose of TCR was reduced in 11 cases (47.8%) after therapeutic IV-MTX administration, and the relative frequency of dose reduction tended to be higher than that of dose increase (median: 37.5% vs. 0.0%, P = 0.0519, permuted Brunner-Munzel test). The magnitude of dose reduction was 18.8% (7.4-50.0%) in the 11 cases with dose reduction. CONCLUSIONS: Therapeutic IV-MTX administration cause a significant increase in C/D, which requires TCR dose reduction. Careful therapeutic drug monitoring of TCR is needed after therapeutic IV-MTX administration in patients receiving immunosuppressive therapy with TCR after allo-HSCT.

A Case of Leg Pain After the Initial Dose of the COVID-19 Vaccine, Followed by Deep Vein Thrombosis and Pulmonary Embolism After the Second Dose.

COVID-19 has been spreading worldwide. Therefore, the COVID-19 vaccine is recommended for prevention. However, adverse events after COVID-19 vaccination remain an issue, and we should monitor patients for adverse events and determine their association with COVID-19 vaccination. Here, we report a case involving a 48-year-old Japanese woman who experienced dull left leg pain that resolved spontaneously after the first vaccine dose, followed by deep vein thrombosis (DVT) and pulmonary embolism (PE) after the second dose. The findings from this case suggest that the COVID-19 vaccine could cause severe adverse events, such as DVT. Therefore, patients should understand their subjective symptoms and report any side effects experienced after the first dose before they take the second dose. Furthermore, medical providers should enquire about all possible symptoms experienced after the initial dose before they administer the second dose.

Enfortumab Vedotin-induced Hyperglycemia and Ileal Conduit Reconstruction-induced Metabolic Acidosis.

We report a 76-year-old man who was treated for hyperglycemia and metabolic acidosis after chemotherapy with enfortumab vedotin and pembrolizumab administered after his surgery for bladder cancer. He had an approximately 20-year history of diabetes. His body mass index was 18.6, and he received metformin 1000 mg/day, sitagliptin 50 mg/day, mitiglinide 30 mg/day, and voglibose 0.6 mg/day with hemoglobin A1c was approximately 7%. He underwent total cystectomy and ileal conduit reconstruction. After relapse, he received chemotherapy but later developed hyperglycemia and metabolic acidosis. His hyperglycemia was caused by enfortumab vedotin, and metabolic acidosis was attributable to the ileocecal canal. These symptoms should be remembered as important complications of this standard treatment, which prompted this case report.

Assessment of Residual Vasospasm in Patients with Plaque Rupture or Plaque Erosion using Optical Coherence Tomography.

AIMS: Coronary vasospasm is associated with acute coronary syndrome (ACS) and may persist during primary percutaneous coronary intervention (PCI). We aimed to elucidate the incidence, morphological characteristics, and prognostic impact of residual vasospasm in plaque rupture (PR) and plaque erosion (PE) lesions using optical coherence tomography (OCT). METHODS: We enrolled 142 patients with ACS who underwent OCT-guided primary PCI. All patients received intracoronary vasodilators before OCT examination. Residual vasospasm was identified as intimal gathering and categorised as polygonal- or wavy- patterned depending on the luminal shape. A wavy pattern was defined as a curved intimal surface line. A polygonal pattern was defined as a lumen with multiple angles. The incidence of major cardiovascular events, defined as death, non-fatal myocardial infarction, stroke, and any revascularization, within 1-year of PCI was identified. RESULTS: The prevalence of residual vasospasm in PR and PE was 15.1% (13 of 86) and 21.4% (12 of 56), respectively. Wavy pattern was the major shape of the residual vasospasm. Polygonal-patterned lumen was more frequently observed in PR than in PE (38.5 vs. 8.3 %). The polygonal-patterned lumens had significantly larger lipid arcs (257.9 vs. 78.0 °; P＜0.01), and significantly smaller areas (1.27 vs. 1.88 mm2; P=0.05) than wavy patterned lumens. Residual vasospasm had a prognostic impact on PR but not PE at 1-year of successful primary PCI. CONCLUSION: Considerable proportion of ACS including both PR and PE had residual vasospasm with variable morphological feature and different prognostic impact.

Diagnosis and Prognostic Value of the Underlying Cause of Acute Coronary Syndrome in Optical Coherence Tomography-Guided Emergency Percutaneous Coronary Intervention.

Background The prognostic impact of optical coherence tomography-diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real-world settings. Methods and Results This investigator-initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography-guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia-driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography-guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One-year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log-rank P<0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log-rank P<0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log-rank P<0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1-year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35-14.89], P=0.014]; PR (HR, 2.18 [95% CI, 1.05-4.53], P=0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause-based optical coherence tomography-guided optimization.