Ten-year trends in lipid management among patients after myocardial infarction in South Korea.

BACKGROUND: Dyslipidemia is an important risk factor for acute myocardial infarction. However, real-world data on its prevalence and lipid management trends for Korean patients with acute myocardial infarction are limited. This study aimed to determine the 10-year temporal trends in dyslipidemia prevalence and lipid management in this patient population. METHODS AND FINDINGS: The study used a merged database of two nationwide observational cohorts (2011-2020) that included 26,751 participants. The primary endpoints were the achievement rates of the (1) absolute low-density lipoprotein cholesterol (LDL-C) target of <70 mg/dL (<1.8 mmol/L), (2) relative LDL-C target reduction of >50% from the baseline, (3) absolute or relative LDL-C target (American target), and (4) both absolute and relative LDL-C targets (European target). The dyslipidemia prevalence increased from 11.1% to 17.1%, whereas the statin prescription rate increased from 92.9% to 97.0% from 2011 to 2020. The rate of high-intensity statin use increased from 12.80% in 2012 to 69.30% in 2020. The rate of ezetimibe use increased from 4.50% in 2016 to 22.50% in 2020. The high-intensity statin and ezetimibe prescription rates (0.20% to 9.30% from 2016 to 2020) increased gradually. The absolute and relative LDL-C target achievement rates increased from 41.4% and 20.8% in 2012 to 62.5% and 39.5% in 2019, respectively. The American (45.7% in 2012 to 68.6% in 2019) and European (16.5% in 2012 to 33.8% in 2019) target achievement rates also increased. CONCLUSIONS: The adoption of lipid management guidelines in clinical practice has improved. However, continued efforts are needed to reduce the risk of recurrent ischemic events.

Widespread Use of Imaging-Guided PCI in Asia: Time for Extended Application.

In recent years, a wealth of clinical data has emerged regarding intravascular imaging involving either intravascular ultrasound or optical coherence tomography. This surge in data has propelled the adoption of intravascular imaging-guided percutaneous coronary intervention (PCI) in daily clinical practice. The findings of current randomized clinical trials regarding imaging guidance have lent strong support to the benefits of intravascular imaging-guided PCI. This holds especially true for the diagnosis and treatment of complex lesions, such as left main disease, diffuse long lesions, chronic total occlusion, severely calcified lesions, bifurcations, and in-stent restenosis, as well as in high-risk patients such as those with acute myocardial infarction or chronic kidney disease. During intravascular imaging-guided PCI, operators attempt to achieve stent optimization for maximized benefits of imaging guidance. This paper provides a comprehensive review on the updated clinical data of intravascular imaging-guided PCI and intravascular ultrasound/optical coherence tomography-derived stent optimization criteria.

The Upper Extremity Lymphatic System Is Not Symmetrical in Individuals: An Anatomic Study Utilizing ICG Lymphography and SPECT/CT Lymphoscintigraphy.

OBJECTIVE: We evaluated whether superficial lymphatic anatomy and functional lymph node drainage are symmetric between the right and left upper extremities of healthy female volunteers, and if handedness is associated with symmetry of superficial lymphatic anatomy. BACKGROUND: Symmetry of lymphatic anatomy has been assumed historically. This assumption of individual anatomic symmetry is being utilized clinically and in research without validation. METHODS: 36 normal female volunteers underwent bilateral indocyanine green (ICG) lymphography and lymphoscintigraphy of the upper extremities. Eight collecting vessel pathways of each upper extremity were mapped on ICG lymphography. 13 lymph node groups were visualized on lymphoscintigraphy. Symmetry of lymphatic anatomy and functional drainage were established by comparing the right and left extremities of each participant. Hand dominance was assessed by hand grip strength on a hand dynamometer. RESULTS: Among the 36 participants, 10 (28%) showed symmetry of all eight upper extremity lymphatic pathways with ICG. However, only 1 (3%) participant demonstrated complete symmetry amongst the 13 lymph node groups. Total symmetry of lymphatic channels was observed on ICG in seven (39%) participants with hand dominance and three (17%) participants without hand dominance (X2 = 2.215, P = 0.137). CONCLUSION: Lymphatic anatomy and functional drainage of the upper extremities are not consistently symmetric. Functional nodal drainage as demonstrated by lymphoscintigraphy shows less symmetry than anatomic studies of lymphatic channels using ICG. Symmetric lymphatic anatomy does not appear to correlate with hand dominance. These findings challenge the prevailing assumption of left-right lymphatic symmetry.

Long-Term Risk of Cardiovascular Death in Patients With Mildly Reduced Ejection Fraction After Acute Myocardial Infarction: A Multicenter, Prospective Registry Study.

BACKGROUND: The prognostic implication of mildly reduced ejection fraction (mrEF) after acute myocardial infarction has not been clearly demonstrated. We investigated the long-term risk of cardiovascular death and its predictors in patients with mrEF following acute myocardial infarction. METHODS AND RESULTS: A total of 18 668 patients who presented with acute myocardial infarction were included in 2 prospective, multicenter registries. The incidence of adverse cardiovascular events according to the left ventricular ejection fraction (EF) strata at index admission were evaluated. A score system consisting of clinical variables were developed to predict long-term cardiovascular death in the mrEF group. There were 2548 patients with reduced EF (EF ≤40%), 4266 patients with mrEF (EF 41%-49%), and 11 854 patients with preserved EF (EF ≥50%). During a median follow-up period of 37.9 months, the cardiovascular death rate was 22.3% in the reduced EF group, 10.3% in the mrEF group, and 7.3% in the preserved EF group (P<0.001). In the mrEF group, age>65 years, hypertension, stroke, severe renal insufficiency, and Killip class ≥3 were independent predictors for cardiovascular death. Presence of >2 predictors best discriminated the high-risk patients for cardiovascular death with an area under the curve of 0.746. Incidence of cardiovascular death in the high-risk mrEF group was comparable with the rEF group, while it was lower in the low-risk mrEF group than in the pEF group. CONCLUSIONS: Patients with mrEF after acute myocardial infarction had a modest risk of cardiovascular death. Clinical predictors could help discriminate a high-risk subpopulation with cardiovascular death risks comparable with those in the reduced EF group.

A Rare Case of X-Linked Four-Way Philadelphia Chromosome Translocation with Therapeutic Challenges and Clonal Evolution.

BACKGROUND: Chronic myeloid leukemia (CML), a myeloproliferative neoplasm defined by the BCR::ABL1 fusion gene arising from the Philadelphia chromosome (Ph) translocation t(9:22)(q34;q11), exhibits diverse clinical courses often influenced by additional chromosomal aberrations (ACAs). This report presents a case of CML har-boring a novel four-way Ph translocation involving the X chromosome, offering insights into the interplay between complex karyotypes and treatment response and emphasizing the need for further research into the role of ACAs in CML management. METHODS: A 42-year-old man diagnosed with CML in the accelerated phase presented a novel four-way Ph translocation involving chromosomes X, 5, 9, and 22: 46,Y,t(X;5;9;22)(q26;q15;q34;q11.2). Despite achieving a major molecular response initially with imatinib and nilotinib, BCR::ABL1 levels (international scale) increased up to 24.0%, which prompted the use of second-line nilotinib. RESULTS: Follow-up bone marrow (BM) studies revealed clonal evolution with trisomy 8 and an unclassified ABL1 mutation (E292V), potentially contributing to resistance. Though a transient major molecular response (MMR) occurred after a switch to third-line dasatinib, this change failed to achieve a deep molecular response, and BCR-ABL1 levels were elevated above the MMR. CONCLUSIONS: This case highlights the challenge of ACAs impacting CML treatment response and prognosis. Limited knowledge exists on complex Ph translocations involving the X chromosome, but this report contributes data for further research. Understanding ACA effects on therapeutic response and prognosis requires a detailed study of such complex chromosomal aberrations.

Unmasking Disparities in Gallbladder Cancer Outcomes in the Disaggregated Asian American Population.

BACKGROUND: Gallbladder cancer (GBC) is associated with a high mortality rate. Asian American (AsA) are among the fastest-growing populations in the United States, yet little is known about the disparity of GBC within this cohort. This study identified trends in treatment and outcomes for GBC in a disaggregated fashion, specifically for this population. METHODS: A retrospective analysis of the National Cancer Database (NCDB) between 2010 and 2019 examining all patients treated for gallbladder cancer was performed. Basic demographic factors were identified for patients of Caucasian, African American, and disaggregated Asian subpopulations. Survival curves were used to identify differences in median overall survival, and a multivariate analysis was performed to determine which factors impact overall survival. RESULTS: A total of 1317 (5%) patients were of AsA origin. Median survival for the overall AsA population is 15.1 months compared with Caucasian (11.5 months) and African Americans (11.4 months) (p < 0.0001). Within the AsA groups, the Korean subpopulation had the lowest survival at 12.6 months, whereas Filipinos had the longest survival at 19.1 months (p < 0.0001). Patients of Filipino descent had the highest rate of surgical resection but lower chemotherapy utilization. Conversely, Korean patients had the highest utilization of multimodality therapy. Multivariate analysis demonstrated that belonging to Chinese, Filipino, or Indian ethnicity was associated with decreased risk of mortality. CONCLUSIONS: There are disparate differences in survival for patients with GBC between AsA groups. Socioeconomic, genetic, and epigenetic factors may influence these differences. Further research is needed to delineate the causes of this disparity.

Glucagon-Like-Peptide-2 Stimulates Lacteal Contractility and Enhances Chylomicron Transport in the Presence of an Intact Enteric Nervous System.

Background and Aims: Secretion and transport of intestinal chylomicrons (CMs) via lymphatics to the blood circulation is stimulated primarily by fat ingestion, whereas several other factors have also been shown to play important roles in regulating CM secretion rate. Among these factors, active regulation of lymphatic pumping has not been appreciated to date. The gut peptide and intestinal growth factor glucagon-like peptide-2 (GLP-2) has emerged as a robust enhancer of intestinal lipid mobilization and secretion. The present study aims to elucidate GLP-2's impact on lacteal contractility and assess enteric nervous system (ENS) involvement in GLP-2-induced effects on lipid mobilization. Methods: Using intravital imaging of a prospero-related homeobox 1-enhanced green fluorescent protein rat model, we assessed GLP-2's effect on lacteal contractility, in the presence and absence of the ENS inhibitor mecamylamine (MEC). Concurrently, to explore the physiological relevance, we examined GLP-2's impact on lymph flow and triglyceride (TG) output in vivo in a rat lymph fistula model. Results: GLP-2 significantly increased lacteal contractility, and this effect was inhibited by MEC. In the rat lymph fistula model, GLP-2 increased lymph flow, lymph volume, cumulative lymph volume, and TG output while reducing lymph TG concentration. MEC administration blocked these effects of GLP-2. Peak enhancement of lacteal contractility and enhancement of lymph flow in vivo occurred simultaneously with maximal effect at 15-20 minutes post GLP-2 administration, suggesting that GLP-2 enhances lipid transport by stimulating lymphatic contractility. Conclusion: For the first time, through imaging and concurrent rat lymphatic fistula studies, we demonstrated active regulation of lymphatic contractility as a key determinant of CM secretion and that intact ENS was required to observe this effect.

Electronic Health Record Nudges and Health Care Quality and Outcomes in Primary Care: A Systematic Review.

Importance: Nudges have been increasingly studied as a tool for facilitating behavior change and may represent a novel way to modify the electronic health record (EHR) to encourage evidence-based care. Objective: To evaluate the association between EHR nudges and health care outcomes in primary care settings and describe implementation facilitators and barriers. Evidence Review: On June 9, 2023, an electronic search was performed in PubMed, Embase, PsycINFO, CINAHL, and Web of Science for all articles about clinician-facing EHR nudges. After reviewing titles, abstracts, and full texts, the present review was restricted to articles that used a randomized clinical trial (RCT) design, focused on primary care settings, and evaluated the association between EHR nudges and health care quality and patient outcome measures. Two reviewers abstracted the following elements: country, targeted clinician types, medical conditions studied, length of evaluation period, study design, sample size, intervention conditions, nudge mechanisms, implementation facilitators and barriers encountered, and major findings. The findings were qualitatively reported by type of health care quality and patient outcome and type of primary care condition targeted. The Risk of Bias 2.0 tool was adapted to evaluate the studies based on RCT design (cluster, parallel, crossover). Studies were scored from 0 to 5 points, with higher scores indicating lower risk of bias. Findings: Fifty-four studies met the inclusion criteria. Overall, most studies (79.6%) were assessed to have a moderate risk of bias. Most or all descriptive (eg, documentation patterns) (30 of 38) or patient-centeredness measures (4 of 4) had positive associations with EHR nudges. As for other measures of health care quality and patient outcomes, few had positive associations between EHR nudges and patient safety (4 of 12), effectiveness (19 of 48), efficiency (0 of 4), patient-reported outcomes (0 of 3), patient adherence (1 of 2), or clinical outcome measures (1 of 7). Conclusions and Relevance: This systematic review found low- and moderate-quality evidence that suggested that EHR nudges were associated with improved descriptive measures (eg, documentation patterns). Meanwhile, it was unclear whether EHR nudges were associated with improvements in other areas of health care quality, such as effectiveness and patient safety outcomes. Future research is needed using longer evaluation periods, a broader range of primary care conditions, and in deimplementation contexts.

Assessing the impact of palatal fistula formation and cleft width on speech outcomes following double opposing Z-plasty in patients with cleft palate.

OBJECTIVE: This retrospective study investigated the influence of palatal fistula (PF) formation after double opposing Z-plasty (DOZ) on speech outcomes in patients with cleft palate (CP), focusing on cleft width and palatal length as predictors of velopharyngeal insufficiency (VPI). METHODS: This study included 1117 patients with CP (579 males, 538 females) who underwent DOZ, performed by a single surgeon, between 1988 and 2017. Demographic characteristics, cleft dimensions, history of PF formation, and speech outcomes were investigated. Speech evaluations were performed at a minimum age of five to assess nasal emission, hypernasality, compensatory articulation, intelligibility, necessity for VPI surgery, and speech therapy. Logistic regression analysis was performed. RESULTS: Speech assessments were conducted at the median age of five (interquartile range [IQR], 5-6 years). Overall, 96.5% of patients achieved 'socially acceptable speech' after DOZ. Patients with PF history showed greater cleft width and experienced higher rates of hypernasality, nasal emission, and VPI on videofluoroscopy (VFS) compared to those without PF history (mean, 11.4 mm vs. 7.1 mm; 28.4% vs. 23.6%; 34.8% vs. 14.9%, 38.5% vs. 14.0%, 40.6% vs. 28.3%, respectively; all p < 0.0001). Cleft width was significantly associated with VPI-related speech outcomes in the multivariate logistic regression analysis, affecting both perceptual and VFS-measured outcomes. CONCLUSIONS: A wider CP gap significantly increased the risk of VPI-related speech difficulties after DOZ. Cleft width is a more critical predictor of adverse speech outcomes than the presence of small-to-medium-sized PFs. Patients with a history of PF and wider cleft gaps require targeted interventions and intensified follow-up to effectively manage and improve speech outcomes.

Optical coherence tomography-guided versus angiography-guided percutaneous coronary intervention for patients with complex lesions (OCCUPI): an investigator-initiated, multicentre, randomised, open-label, superiority trial in South Korea.

BACKGROUND: Despite the detailed imaging information provided by optical coherence tomography (OCT) during percutaneous coronary intervention (PCI), clinical benefits of this imaging technique in this setting remain uncertain. The aim of the OCCUPI trial was to compare the clinical benefits of OCT-guided versus angiography-guided PCI for complex lesions, assessed as the rate of major adverse cardiac events at 1 year. METHODS: This investigator-initiated, multicentre, randomised, open-label, superiority trial conducted at 20 hospitals in South Korea enrolled patients aged 19-85 years for whom PCI with drug-eluting stents was clinically indicated. After diagnostic angiography, clinical and angiographic findings were assessed to identify patients who met the criterion of having one or more complex lesions. Patients were randomly assigned 1:1 to receive PCI with OCT guidance (OCT-guidance group) or angiography guidance without OCT (angiography-guidance group). Web-response permuted-block randomisation (mixed blocks of four or six) was used at each participating site to allocate patients. The allocation sequence was computer-generated by an external programmer who was not involved in the rest of the trial. Outcome assessors were masked to group assignment. Patients, follow-up health-care providers, and data analysers were not masked. PCI was done according to conventional standard methods with everolimus-eluting stents. The primary endpoint was major adverse cardiac events (a composite of cardiac death, myocardial infarction, stent thrombosis, or ischaemia-driven target-vessel revascularisation), 1 year after PCI. The primary analysis was done in the intention-to-treat population. The margin used to establish superiority was 1·0 as a hazard ratio. This trial is registered with ClinicalTrials.gov (NCT03625908) and is completed. FINDINGS: Between Jan 9, 2019, and Sept 22, 2022, 1604 patients requiring PCI with drug-eluting stents for complex lesions were randomly assigned to receive either OCT-guided PCI (n=803) or angiography-guided PCI (n=801). 1290 (80%) of 1604 patients were male and 314 (20%) were female. The median age of patients at randomisation was 64 years (IQR 57-70). 1588 (99%) patients completed 1-year follow-up. The primary endpoint occurred in 37 (5%) of 803 patients in the OCT-guided PCI group and 59 (7%) of 801 patients in the angiography-guided PCI group (absolute difference -2·8% [95% CI -5·1 to -0·4]; hazard ratio 0·62 [95% CI 0·41 to 0·93]; p=0·023). Rates of stroke, bleeding events, and contrast-induced nephropathy were not significantly different across the two groups. INTERPRETATION: Among patients who required drug-eluting stent implantation for complex lesions, OCT guidance resulted in a lower incidence of major adverse cardiac events at 1 year compared with angiography guidance. These findings indicate the existence of a therapeutic benefit of OCT as an intravascular imaging technique for PCI guidance in patients with complex coronary lesions. FUNDING: Abbott Vascular and Cardiovascular Research Center. TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.

Effects of Mixed Metal Exposure on MRI Metrics in Basal Ganglia.

Welding fumes contain various metals. Past studies, however, mainly focused on Manganese (Mn)-related neurotoxicity. This study investigated welding-related mixed metal exposure effects on MRI metrics in the basal ganglia (BG) and their dose-response relationship. Subjects with (N = 23) and without (N = 24) a welding exposure history were examined. Metal exposure was estimated with exposure history questionnaire and whole blood metal levels. T1 (weighted-intensity and relaxation time; estimates of brain Mn accumulation), diffusion tensor imaging [Axial (AD), mean (MD), radial diffusivity (RD), and fractional anisotropy (FA); estimates of microstructural differences] metrics in BG [caudate nucleus, putamen, and globus pallidus (GP)] and voxel-based morphometry (for volume) were examined and related with metal exposure measures. Compared to controls, welders showed higher GP R1 (1/T1; p = 0.034) but no differences in blood metal and T1-weighted (T1W) values in any ROIs (p's > 0.120). They also had higher AD and MD values in the GP (p's < 0.033) but lower FA values in the putamen (p = 0.039) with no morphologic differences. In welders, higher blood Mn and Vanadium (V) levels predicted higher BG R1 and T1W values (p's < 0.015). There also were significant overall metal mixture effects on GP T1W and R1 values. Moreover, GP AD and MD values showed non-linear associations with BG T1W values: They increased with increasing T1W values only above certain threshold of T1 values. The current findings suggest that Mn and V individually but also metal mixtures jointly predict GP T1 signals that may in turn contribute to altered DTI metrics in the BG after certain exposure threshold levels.

Endoscopic repair of duodenal perforations, a scoping review.

BACKGROUND: There is a discrepancy in the surgical and endoscopic literature for managing duodenal perforations. Although often managed conservatively, surgical repair is the standard treatment for duodenal perforations. This contrasts with the gastroenterology literature, which now recommends endoscopic repair of duodenal perforations, which are more frequently iatrogenic from the growing field of advanced endoscopic procedures. This study aims to provide a scoping review to summarize the current literature content and quality on endoscopic repair of duodenal perforations. METHODS: The protocol for performing this scoping review was outlined by the Joanna Briggs Institute. All studies that reported primary outcomes of patients who had undergone endoscopic repair of duodenal perforations before February 2022, regardless of perforation etiology or repair type were reviewed, with studies after 1999 meeting inclusion criteria. The study excluded articles that did not report clinical outcomes of endoscopic repair, articles that did not describe where in the gastrointestinal tract the endoscopic repair occurred, pediatric patients, and animal studies. RESULTS: 7606 abstracts were screened, with 474 full articles reviewed and 152 studies met inclusion criteria. 560 patients had duodenal perforations repaired endoscopically, with a technical success rate of 90.4% and a survival rate of 86.7%. Most of these perforations (74.5%) were iatrogenic from endoscopic procedures or surgery. Only one randomized control trial (RCT) was found, and 53% of studies were case reports. CONCLUSION: These results suggest that endoscopic repair could emerge as a viable first-line treatment for duodenal perforation and highlight the need for more high-quality research in this topic.

Optimal timing of revascularization for patients with non-ST segment elevation myocardial infarction and severe left ventricular dysfunction.

Optimal timing of revascularization for patients who presented with non-ST segment elevation myocardial infarction (NSTEMI) and severe left ventricular (LV) dysfunction is unclear. A total of 386 NSTEMI patients with severe LV dysfunction from the nationwide, multicenter, and prospective Korea Acute Myocardial Infarction Registry V (KAMIR-V) were enrolled. Severe LV dysfunction was defined as LV ejection fraction ≤ 35%. Patients with cardiogenic shock were excluded. Patients were stratified into two groups: PCI within 24 hours (early invasive group) and PCI over 24 hours (selective invasive group). Primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) including all-cause death, non-fatal MI, repeat revascularization, and stroke at 12 months after index procedure. Early invasive group showed higher incidence of in-hospital death (9.4% vs 3.3%, P = .036) and cardiogenic shock (11.5% vs 4.6%, P = .030) after PCI. Early invasive group also showed higher maximum troponin I level during admission (27.7 ±â€…44.8 ng/mL vs 14.9 ±â€…24.6 ng/mL, P = .001), compared with the selective invasive group. Early invasive group had an increased risk of 12-month MACCE, compared with selective invasive group (25.6% vs 17.1%; adjusted HR = 2.10, 95% CI 1.17-3.77, P = .006). Among NSTEMI patients with severe LV dysfunction, the early invasive strategy did not improve the clinical outcomes. This data supports that an individualized approach may benefit high-risk NSTEMI patients rather than a routine invasive approach.

In Silico Analysis and Biochemical Characterization of Streptomyces PET Hydrolase with Bis(2-Hydroxyethyl) Terephthalate Biodegradation Activity.

Polyethylene terephthalate (PET), one of the most widely used plastics in the world, causes serious environmental problems. Recently, scientists have been focused on the enzymatic degradation of PET, an environmentally friendly method that offers an attractive approach to the degradation and recycling of PET. In this work, PET hydrolase from Streptomyces sp. W2061 was biochemically characterized, and the biodegradation of PET was performed using the PET model substrate bis (2-hydroxyethyl terephthalate) (BHET). PET hydrolase has an isoelectric point of 5.84, and a molecular mass of about 50.31 kDa. The optimum pH and temperature were 7.0 and 40°C, respectively. LC-MS analysis of the enzymatic products showed that the PET hydrolase successfully degraded a single ester bond of BHET, leading to the formation of MHET. Furthermore, in silico characterization of the PET hydrolase protein sequence and its predicted three-dimensional structure was designed and compared with the well-characterized IsPETase from Ideonella sakaiensis. The structural analysis showed that the (Gly-x1-Ser-x2-Gly) serine hydrolase motif and the catalytic triad (Ser, Asp, and His) were conserved in all sequences. In addition, we integrated molecular dynamics (MD) simulations to analyze the variation in the structural stability of the PET hydrolase in the absence and presence of BHET. These simulations showed the formation of a stable complex between the PET hydrolase and BHET. To the best of our knowledge, this is the first study on Streptomyces sp. W2061 to investigate the BHET degradation activity of PET hydrolase, which has potential application in the biodegradation of plastics in the environment.

Sociodemographic and Clinical Characteristics Associated with Genetic Testing among Cancer Survivors: Evidence from Three Cancer Registries.

INTRODUCTION: Genetic tests, including germline and tumor (somatic) testing, can optimize the clinical care and outcomes for cancer patients and their family members. However, evidence on cancer patients' use of genetic testing and discussions about it with healthcare providers is limited. METHODS: Study participants included cancer survivors aged 18 or older, drawn from the 2021 Health Information and National Trends Survey (HINTS)-Surveillance, Epidemiology, and End Results (SEER) linked database, which comprises three US cancer registries: Iowa, New Mexico, and the Greater Bay Area. Sociodemographic factors (e.g., age, sex, income, education) at the time of the survey and clinical characteristics (e.g., cancer site, stage) at the time of diagnosis were compared based on self-reported genetic testing status and provider discussions, using survey design-adjusted analysis. RESULTS: The weighted study sample comprised 415,978 cancer survivors with a mean age of 70.5 years at the time of the survey. Overall, 17.0% reported having germline testing, 8.5% having tumor testing, and 8.6% discussing tumor testing with their healthcare providers. Higher proportions of germline genetic testing were observed among survivors under age 65 at the time of the survey, females, holding college degrees, and with private insurance coverage compared to their respective counterparts - males, aged 65 or above when surveyed, with lower educational attainment, and with public insurance or uninsured. The proportion of those who reported tumor testing was greater for those diagnosed in recent years (2015-2017 vs. before 2002). Regarding clinical characteristics, survivors with ovarian and breast cancers had a 7.0-36.4% higher prevalence of both testing compared to those with other cancer types lacking germline indication. More cancer survivors diagnosed at distant stages (vs. regional) or between 2015 and 2017 (vs. 2003-2010) reported having provider discussions about tumor testing. CONCLUSION: Findings showed that the highest reports of germline testing were among young female cancer survivors and those with higher education and private insurance. Survivors diagnosed in recent years or with advanced-stage disease were more likely to report discussing tumor testing with providers. Further research is warranted to better understand the barriers and educational needs of cancer patients, caregivers, and providers to optimize genetic testing strategies.

Enhanced Lung Cancer Detection Using a Combined Ratio of Antigen-Autoantibody Immune Complexes against CYFRA 21-1 and p53.

The early detection of lung cancer (LC) improves patient outcomes, but current methods have limitations. Autoantibodies against tumor-associated antigens have potential as early biomarkers. This study evaluated the 9G testTM Cancer/Lung, measuring circulating complexes of two antigen-autoantibody immune complexes (AIC) against their respective free antigens (CYFRA 21-1 and p53) for LC diagnosis. We analyzed 100 LC patients and 119 healthy controls using the 9G testTM Cancer/Lung, quantifying the levels of AICs (CYFRA 21-1-Anti-CYFRA 21-1 autoantibody immune complex (CIC) and p53-Anti-p53 autoantibody immune complex (PIC)), free antigens (CYFRA 21-1 and p53), and ratios of AICs/antigens (LC index). The levels of the CICs and PICs were significantly elevated in LC compared to the controls (p < 0.0062 and p < 0.0026), while free antigens showed no significant difference. The CIC/CYFRA 21-1 and PIC/p53 ratios were also significantly higher in LC (all, p < 0.0001). The LC index, when combining both ratios, exhibited the best diagnostic performance with an area under the curve (AUC) of 0.945, exceeding individual CICs, PICs, and free antigens (AUCs ≤ 0.887). At a cut-off of 3.60, the LC index achieved 81% sensitivity and 95% specificity for LC diagnosis. It detected early-stage (Stage I-II) LC with 87.5% sensitivity, exceeding its performance in advanced stages (72.7%). The LC index showed no significant differences based on age, gender, smoking status (former, current, or never smoker), or pack years smoked. The LC index demonstrates promising potential for early LC diagnosis, exceeding conventional free antigen markers.

Pre-Hospital Delay and Outcomes in Myocardial Infarction With Nonobstructive Coronary Arteries.

BACKGROUND AND OBJECTIVES: Real-world evidence on the relationship between delayed hospitalization and outcomes in myocardial infarction with nonobstructive coronary arteries (MINOCA) is lacking. Hence, we aimed to evaluate the clinical characteristics of patients with MINOCA and the 2-year mortality outcomes in this patient population according to the symptom-to-door time (SDT). METHODS: Overall, 861 patients with MINOCA from 2 Korean nationwide observational registries (2011-2020) were included and categorized as early or late presenters. Late presentation was defined as SDT ≥12 hours in patients with ST-segment elevation myocardial infarction (STEMI) and SDT ≥24 hours in patients with non-STEMI. The primary outcome was 2-year all-cause mortality. Propensity score matching (PSM) and age-sex adjusted analysis were used to determine whether late presentation independently affected mortality. Multivariate logistic regression analysis was used to examine the independent factors correlated with late presentation. RESULTS: In unadjusted data, late presenters had a notably higher risk of 2-year all-cause mortality than early presenters (hazard ratio [HR], 2.44; 95% confidence interval [CI], 1.47-4.08). This trend persisted in age-sex adjusted analysis (adjusted HR, 2.29; 95% CI, 1.36-3.84) and PSM-adjusted analysis (adjusted HR, 2.18; 95% CI, 1.05-4.53). The positive independent factors for late presentation included female sex, no emergency medical service use and high creatinine level, whereas the negative independent factor was a dyslipidemia. CONCLUSIONS: Late presentation is associated with higher mortality in patients with MINOCA. Multidisciplinary efforts are needed to reduce pre-hospital delay, thereby improving the clinical outcomes in these patients.

Enhancing Familial Hypercholesterolemia Detection in South Korea: A Targeted Screening Approach Integrating National Program and Genetic Cascade Screening.

BACKGROUND AND OBJECTIVES: Familial hypercholesterolemia (FH) increases the risk of premature cardiovascular disease through disrupted low-density lipoprotein cholesterol (LDL-C) metabolism. Although FH is a severe condition, it remains widely underdiagnosed, which can be attributed to barriers in genetic testing and a lack of awareness. This study aims to propose and evaluate a targeted screening program for FH in South Korea by integrating the General Health Screening Program (GHSP) with cascade genetic screening. METHODS: The study included individuals with LDL-C levels ≥190 mg/dL identified during the 2021 GHSP (primary participants). Data on demographics, lifestyle, medical history, and family history were collected through questionnaires. Targeted next-generation sequencing was used to identify pathogenic mutations in the PCSK9, APOB, LDLRAP1, and LDLR genes associated with FH. Pathogenic mutations found in primary participants were confirmed in their relatives (secondary participants) using Sanger sequencing. Participant characteristics were analyzed based on the presence of pathogenic mutations. RESULTS: Among 83 individuals with severe hypercholesterolemia identified through the GHSP, 7 primary participants (8.4%) carried pathogenic mutations in the LDLR and PCSK9 genes. In secondary participants, pathogenic mutations were identified in 61.1% of the relatives of 4 patients with pathogenic mutations. The prevalence of pathogenic mutations was significantly higher in primary participants compared to secondary participants. CONCLUSIONS: Integrating community resources with FH screening can enhance the early detection and treatment of FH. By utilizing GHSP data and adding genetic screening, the proposed model provides a strategy to reduce the cardiovascular risks associated with FH, supporting its wider adoption at the national level.

Advanced Mechanical Transfer of Micro-LEDs Enabled by Structurally Modified Wide Sapphire Nanomembranes through Thermal Reflow of Photoresist.

Micro light-emitting diodes (micro-LEDs) are pivotal in next-generation display technologies, driven by the need for high pixel density. This study introduces a novel methodology utilizing wide sapphire nanomembranes (W-SNM) as a dual-purpose template for high-quality epitaxial growth and the mechanical lift-off of individual micro-LEDs. Micro-LEDs grow individually on W-SNM, obviating the chip singulation process. By employing mechanical fracturing of the thin W-SNM, our method facilitates the transfer of micro-LEDs without the conventional laser lift-off (LLO) process. Previously introduced sapphire nanomembranes (SNM) have shown promise in enhancing epitaxial layer quality; however, they encountered challenges in managing micro-LED size variation and achieving efficient mechanical transfer. Here, we apply simple yet effective adjustments to the SNM structure, specifically, its elevation and widening. This strategic modification allows micro-LEDs to endure applied forces without incurring cracks or defects, ensuring that only the targeted W-SNM are selectively fractured. The mechanically transferred vertical 15 × 15 µm2 micro-LED device operates at an optimal turn-on voltage of 3.3 V. Finite element simulations validate the mechanical strain distribution between the W-SNM and GaN when pressure is applied, confirming the efficacy of our design approach. This pioneering methodology offers a streamlined, efficient pathway for the production and mechanical transfer of micro-LEDs, presenting new avenues for their integration into next-generation, high-performance displays.