Optimal Antithrombotic Therapy Beyond 1-Year After Coronary Revascularization in Patients With Atrial Fibrillation.

BACKGROUND: Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond one year after coronary revascularization. The aim of this study was to compare the outcomes between NOAC monotherapy and NOAC plus antiplatelet combination therapy using real-world data. METHODS: Between 2015 and 2020, patients with AF who had received NOACs beyond one year after coronary revascularization were enrolled from Korean national insurance data. We emulated a pragmatic sequence of trials between the NOAC monotherapy and the antiplatelet combination therapy followed by propensity score matching. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. RESULTS: Among 206,407 person-trials from 4,465 individuals, we compared 3,275 pairs of the monotherapy and the matched combination therapy. During a median follow-up of 1.24 years, the incidence rate of MACCE was 19.4% and 20.0% per patient-year in the monotherapy group and the antiplatelet combination group, respectively (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88-1.05; P = 0.422). Compared with the antiplatelet combination group, the monotherapy group had a significantly lower incidence rate of major bleeding, defined as intracranial bleeding or gastrointestinal bleeding requiring hospitalization (2.8% vs. 3.6% per patient-year; HR, 0.78; 95% CI, 0.62-0.97; P = 0.024). CONCLUSION: As an antithrombotic therapy for AF beyond one year after coronary revascularization, NOAC monotherapy was associated with a similar risk of MACCE and a lower risk of major bleeding compared to NOAC plus antiplatelet combination therapy.

Ovarian Metastasis from Human Papillomavirus-associated Usual-type Endocervical Adenocarcinoma: Clinicopathological Characteristics for Distinguishing from Primary Ovarian Mucinous or Endometrioid Tumor.

BACKGROUND/AIM: Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA. PATIENTS AND METHODS: Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed. RESULTS: Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up. CONCLUSION: Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.

Outcomes of Colorectal Endoscopic Submucosal Dissection According to the Size of Colorectal Neoplasm: A HASID Multicenter Study.

BACKGROUND/AIM: Endoscopic submucosal dissection (ESD) is a valuable technique for treating colorectal neoplasms. However, there are insufficient data concerning the treatment outcomes in relation to the size of colorectal neoplasms. PATIENTS AND METHODS: The data on ESD for colorectal epithelial neoplasms between January 2015 and December 2020 were retrospectively collected from five tertiary medical centers. Colorectal neoplasms were stratified into groups based on their longitudinal diameter: <20 mm as Group 1, 20-39 mm as Group 2, 40-59 mm as Group 3, and 60 mm or more as Group 4. RESULTS: Of the 1,446 patients, 132 patients were in Group 1 (<20 mm), 1,022 in Group 2 (20-39 mm), 249 in Group 3 (40-59 mm), and 43 in Group 4 (≥60 mm). There was an observed trend of increasing age from Group 1 to Group 4, accompanied by a corresponding increase in the Charlson Comorbidity Index. Procedure time also exhibited a gradual increase from Group 1 to Group 4. Similarly, the length of hospital stay tended to increase from Group 1 to Group 4. The predictive model, using restricted cubic spline curves, revealed that as the size of lesion exceeded 30 mm, complete resection steadily decreased, and major complications notably increased. CONCLUSION: As the size of colorectal neoplasms increases, the rate of complete resection decreases and the rate of complications increases.

Differences in cognitive trajectories of dementia: Comparison Alzheimer's disease dementia and Dementia with Lewy bodies in Korean patient cohort.

BACKGROUND AND PURPOSE: Prediction of the dementia progression is important for patient management. We aimed to investigate the cognitive trajectories of Alzheimer's disease dementia (ADD) and dementia with Lewy bodies (DLB) according to the initial structural change measured by comprehensive visual rating scales (CVRS). Methods We retrospectively included the patients who initially visited the Dementia Clinic of Chonnam National University Hospital between 2010 to 2012. All patients underwent dementia work up including neuropsychological battery (Seoul Neuropsychological Screening Battery, SNSB). We recruited the participant who underwent SNSB annually for three years successively. Total 136 patients of ADD and 63 patients of DLB were included for analyze. We analyzed the decline pattern of cognitive profile according to the initial brain structural changes. Results The general cognitive trajectories between ADD and DLB patients were not different. However, DLB patients showed more rapid decline of cognitive function in language and related function, visual memory function, and frontal executive function. The scores were lower in participants with DLB with lesser atrophy group in attention, visuospatial function, and frontal executive function. In analysis of the cognitive trajectories, the visual memory domain declined rapidly in DLB with lesser atrophy group compared with the ADD with lesser atrophy group. Conclusion We founded that the differences in visual cognitive profile in ADD and DLB patients in serial follow up of neuropsychological tests. It is prominent in the mild structural change group of ADD and DLB.

The Influence of Fatigue, Recovery, and Environmental Factors on the Body Stability of Construction Workers.

In the construction industry, falls, slips, and trips (FST) account for 42.3% of all accidents. The primary cause of FST incidents is directly related to the deterioration of workers' body stability. To prevent FST-related accidents, it is crucial to understand the interaction between physical fatigue and body stability in construction workers. Therefore, this study investigates the impact of fatigue on body stability in various construction site environments using Dynamic Time Warping (DTW) analysis. We conducted experiments reflecting six different fatigue levels and four environmental conditions. The analysis process involves comparing changes in DTW values derived from acceleration data obtained through wearable sensors across varying fatigue levels and construction environments. The results reveal the following changes in DTW values across different environments and fatigue levels: for non-obstacle, obstacle, water, and oil conditions, DTW values tend to increase as fatigue levels rise. In our experiments, we observed a significant decrease in body stability against external environments starting from fatigue Levels 3 or 4 (30% and 40% of the maximum failure point). In the non-obstacle condition, the DTW values were 9.4 at Level 0, 12.8 at Level 3, and 23.1 at Level 5. In contrast, for the oil condition, which exhibited the highest DTW values, the values were 10.5 at Level 0, 19.1 at Level 3, and 34.5 at Level 5. These experimental results confirm that the body stability of construction workers is influenced by both fatigue levels and external environmental conditions. Further analysis of recovery time, defined as the time it takes for body stability to return to its original level, revealed an increasing trend in recovery time as fatigue levels increased. This study quantitatively demonstrates through wearable sensor data that, as fatigue levels increase, workers experience decreased body stability and longer recovery times. The findings of this study can inform individual worker fatigue management in the future.

Anticoagulants are a risk factor for delayed bleeding after colorectal endoscopic submucosal dissection: A HASID multicenter study.

INTRODUCTION: Delayed bleeding is an important adverse event following colorectal endoscopic submucosal dissection (ESD). However, whether anticoagulants are risk factors for delayed bleeding after colorectal ESD remains debatable. METHODS: We retrospectively analyzed 1,708 patients who underwent colorectal ESDs between January 2015 and December 2020 at five academic medical centers in South Korea. We aimed to identify the risk factors for delayed bleeding in patients after colorectal ESD and, in particular, to evaluate the effect of anticoagulants. RESULTS: Delayed bleeding occurred in 40 of 1,708 patients (2.3 %). The risk factors for delayed bleeding were antithrombotic agents (odds ratio [OR], 6.155; 95% confidence interval [CI], 3.201-11.825; p < 0.001), antiplatelet agents (OR, 4.609; 95% CI, 2.200-9.658; p < 0.001), anticoagulants (OR, 8.286; 95% CI, 2.934-23.402; p < 0.001), and tumor location in the rectum (OR, 2.055; 95% CI, 1.085-3.897; p = 0.027). In the analysis that excluded patients taking antiplatelet agents, the delayed bleeding rate was higher in patients taking anticoagulants (1.6% no antithrombotic agents vs. 12.5% taking anticoagulants, p < 0.001). There was no difference in the delayed bleeding rate (4.2% direct oral anticoagulants vs. 25.0% warfarin, p = 0.138) or clinical outcomes according to the type of anticoagulant used. CONCLUSIONS: Anticoagulants use was a risk factor for delayed bleeding after colorectal ESD, and there was no difference in the risk of delayed bleeding based on the type of anticoagulant used. Colorectal ESD in patients receiving anticoagulants requires careful observation and management for delayed bleeding.

Efficient Production of Enterovirus 71 (EV71) Virus-like Particles by Controlling Promoter Strength in Insect Cells.

This study was conducted to efficiently produce virus-like particles (VLPs) of enterovirus 71 (EV71), a causative virus of hand, foot, and mouth disease (HFMD). The expression level of the P1 precursor, a structural protein of EV71, was modified to increase VLP production, and the optimal expression level and duration of the 3CD protein for P1 cleavage were determined. The expression level and duration of 3CD were controlled by the p10 promoter, which was weakened by repeated burst sequence (BS) applications, as well as the OpIE2 promoter, which was weakened by the insertion of random untranslated region sequences of various lengths. The cleavage and production efficiency of the P1 precursor were compared based on the expression time and level of 3CD, revealing that the p10-BS5 promoter with four repeated BSs was the most effective. When P1 and 3CD were expressed using the hyperexpression vector and the p10-BS5 promoter, high levels of structural protein production and normal HFMD-VLP formation were observed, respectively. This study suggests that the production efficiency of HFMD-VLPs can be significantly enhanced by increasing the expression of the P1 precursor and controlling the amount and duration of 3CD expression.

Age-related Differences in Spatially Resolved Transcriptomic Profiles of Patients With Hormone Receptor-positive Breast Carcinoma.

BACKGROUND/AIM: Patients' age may influence the response to chemotherapy and the clinical course of breast carcinoma. This study aimed to compare the spatial transcriptomic profiles between younger (≤50 years) and older (>50 years) patients with hormone receptor (HR)-positive breast carcinoma. PATIENTS AND METHODS: Seven cases of breast carcinoma were included. We performed digital spatial profiling and bioinformatic analysis to investigate the spatial transcriptomes of the epithelial and stromal compartments. RESULTS: In the epithelial compartment of three young-age breast carcinoma (YABC) cases, we found 21 up-regulated and 7 down-regulated genes. The top two most up-regulated genes were serpin peptidase inhibitor clade A member 1 and serine protease. The gene ontology enrichment analysis revealed a significant up-regulation of genes defining ribosomal structures and functions in YABCs. The gene set enrichment analysis revealed that gene sets defining early and late responses to estrogen, response to interferon-α, and tumor necrosis factor-α signaling were significantly enriched in YABCs. CONCLUSION: We described for the first time the age-related differences in spatially resolved transcriptomic profiles and up-regulated transcriptional pathways of HR-positive breast carcinoma. Our observations highlight the critical need for age-specific treatment strategies for breast carcinoma management.

Histopathologic image-based deep learning classifier for predicting platinum-based treatment responses in high-grade serous ovarian cancer.

Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

Trends in Dual Antiplatelet Therapy of Aspirin and Clopidogrel and Outcomes in Ischemic Stroke Patients Noneligible for POINT/CHANCE Trial Treatment.

BACKGROUND: Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated. METHODS AND RESULTS: In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 (Ptrend<0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets. CONCLUSIONS: Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.

Clinical outcomes of colorectal neoplasm with positive resection margin after endoscopic submucosal dissection.

A positive resection margin after colorectal endoscopic submucosal dissection (ESD) is associated with an increased risk of recurrence. We aimed to identify the clinical significance of positive resection margins in colorectal neoplasms after ESD. We reviewed 632 patients who had en bloc colorectal ESD at two hospitals between 2015 and 2020. The recurrence rates and presence of residual tumor after surgery were evaluated. The rate of additional surgery after ESD and recurrence rate were significantly higher in patients with incomplete resection (n = 75) compared to patients with complete resection (n = 557). When focusing solely on non-invasive lesions, no significant differences in recurrence rates were observed between the groups with complete and incomplete resection (0.2% vs. 1.9%, p = 0.057). Among 84 patients with submucosal invasive carcinoma, 39 patients underwent additional surgery due to non-curative resection. Positive vertical margin and lymphovascular invasion were associated with residual tumor. Lymphovascular invasion was associated with lymph node metastasis. However, no residual tumor nor lymph node metastases were found in patients with only one unfavorable histological factor. In conclusion, a positive resection margin in non-invasive colorectal lesions, did not significantly impact the recurrence rate. Also, in T1 colorectal cancer with a positive vertical resection margin, salvage surgery can be considered in selected patients with additional risk factors.

Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes.

BACKGROUND/AIMS: Bile reflux (BR) can influence the gastric environment by altering gastric acidity and possibly the gastric microbiota composition. This study investigated the correlation between bile acids and microbial compositions in the gastric juice of 50 subjects with differing gastric pathologies. METHODS: This study included 50 subjects, which were categorized into three groups based on the endoscopic BR grading system. The primary and secondary bile acid concentrations in gastric juice samples were measured, and microbiota profiling was conducted using 16 S rRNA gene sequencing. RESULTS: Significant differences were observed in each bile acid level in the three endoscopic BR groups (P < 0.05). The Shannon index demonstrated a significant decrease in the higher BR groups (P < 0.05). Analysis of the ß-diversity revealed that BR significantly altered the gastric microbiota composition. The presence of neoplastic lesions and the presence of H. pylori infection impacted the ß-diversity of the gastric juice microbiota. The abundance of the Streptococcus and Lancefielfdella genera exhibited positive correlations for almost all bile acid components(P < 0.05). In addition, the abundance of Slobacterium, Veillonella, and Schaalia showed positive correlations with primary unconjugated bile acids (P < 0.05). CONCLUSION: Changes in microbial diversity in the gastric juice were associated with BR presence in the stomach. This result suggests that the degree of BR should be considered when studying the gastric juice microbiome.

Applicability of selected reaction monitoring for precise screening tests.

INTRODUCTION: The proactive identification of diseases through screening tests has long been endorsed as a means to preempt symptomatic onset. However, such screening endeavors are fraught with complications, such as diagnostic inaccuracies, procedural risks, and patient unease during examinations. These challenges are amplified when screenings for multiple diseases are administered concurrently. Selected Reaction Monitoring (SRM) offers a unique advantage, allowing for the high-throughput quantification of hundreds of analytes with minimal interferences. AREAS COVERED: Our research posits that SRM-based assays, traditionally tailored for single-disease biomarker profiling, can be repurposed for multi-disease screening. This innovative approach has the potential to substantially alleviate time, labor, and cost demands on healthcare systems and patients alike. Nonetheless, there are formidable methodological hurdles to overcome. These include difficulties in detecting low-abundance proteins and the risk of model overfitting due to the multiple functionalities of single proteins across different disease spectrums - issues especially pertinent in blood-based assays where detection sensitivity is constrained. As we move forward, technological strides in sample preparation, online extraction, throughput, and automation are expected to ameliorate these limitations. EXPERT OPINION: The maturation of mass spectrometry's integration into clinical laboratories appears imminent, positioning it as an invaluable asset for delivering highly sensitive, reproducible, and precise diagnostic results.

Diagnostic Value of Immunostaining for Thyroid Transcription Factor 1 (TTF1) and Paired Box 8 (PAX8) in Distinguishing Pulmonary Metastases of Mesonephric and Mesonephric-like Adenocarcinomas from Primary Lung Adenocarcinomas.

BACKGROUND/AIM: Both mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) express thyroid transcription factor 1 (TTF1). TTF1 is also considered a highly sensitive and specific diagnostic marker for primary lung adenocarcinoma (PLA). However, distinguishing PLA from pulmonary metastatic MA/MLA (PMM) based on the expression of TTF1 alone can be difficult. This study aimed to investigate the expression of TTF1 and paired box 8 (PAX8) and assess their value in distinguishing PMM from PLA. PATIENTS AND METHODS: We reviewed the electronic medical records and pathology slides of eight PMM cases. We conducted immunostaining for TTF1 and PAX8 in 6, 8, and 21 cases of primary MA/MLA, PMM, and PLA, respectively. RESULTS: Two patients with stage IB uterine MLA developed lung metastases at 5 and 57 months after hysterectomy. Solitary pulmonary nodules were suspected to be primary lung cancer in two patients. Compared to primary tumors, all matched PMMs exhibited reduced TTF1 immunoreactivity. In contrast, the majority of PLAs showed uniform and intense TTF1 expression. All except one PMM exhibited diffuse and strong PAX8 expression, while only one PLA showed focal and weak PAX8 expression. CONCLUSION: Immunostaining for TTF1 and PAX8 can help in distinguishing PMM from PLA in the diagnosis of pulmonary lesions detected in patients with a history of MA/MLA.

Outcomes of Colorectal Endoscopic Submucosal Dissection for Elderly Patients: A Multicenter Study by the Honam Association for the Study of Intestinal Disease (HASID).

BACKGROUND/AIM: The aging population has been growing gradually; therefore, the proportion of elderly patients undergoing colorectal endoscopic submucosal dissection (ESD) has also been increasing. However, there is a lack of large-scale studies on the efficacy and safety of colorectal ESD in elderly patients. PATIENTS AND METHODS: This retrospective analysis evaluated colorectal ESDs performed at five tertiary medical institutions between January 2015 and December 2020. Patients were categorized into the following four age groups: Middle-aged (<65 years), young-elderly (≥65 to <75 years), mid-elderly (≥75 to <85 years), and very elderly (≥85 years). Of the 1,446 patients included, 668 (46.2%), 466 (32.2%), 293 (20.3%), and 19 (1.3%) were in the middle-aged, young-elderly, mid-elderly, and very-elderly groups, respectively. RESULTS: Compared to younger patients, more older patients used aspirin, clopidogrel, and anti-thrombotic agents. Additionally, the Charlson comorbidity index increased significantly with increasing age. However, no significant differences were observed in the complete resection rates nor the rates of complications, such as perforation, bleeding, and post-ESD coagulation syndrome, among the different age groups. A restricted cubic spline curve was used to construct predictive models for complete resection and major complications based on age and showed that the need for complete resection did not decrease with increasing age. Furthermore, major complications did not significantly differ with age progression. CONCLUSION: Colorectal ESD should be actively considered as a relatively safe and effective treatment method for elderly patients.

Predictive factors associated with technical difficulty in colorectal endoscopic submucosal dissection: A Honam Association for the Study of Intestinal Disease (HASID) multicenter study.

Colorectal endoscopic submucosal dissection (ESD) is a promising but challenging procedure. It is not widely performed due to its technical difficulty. We aimed to find the predictive factors associated with technical difficulty in colorectal ESD before the procedure. Clinical data from patients who underwent ESD for colorectal tumors in 5 hospitals in Honam province of South Korea between 2015 and 2020 were reviewed retrospectively. Technically difficult colorectal ESD procedure was defined in 3 points. Long procedure time (longer than 60 minutes), occurrence of perforation, and failure of en bloc resection. Factors associated with technically difficult ESD were included as main outcome measure. 1446 patients were identified and their data were analyzed. Median procedure time was 30.0 minutes and median long axis of the tumor was 20.1 mm. Technically difficult procedures including long procedure time were 231 cases (16.0%), perforation occurred in 34 cases (2.3%), and en bloc resection was done in 1292 cases (89.3%). Tumor size larger than 35 mm (odd ratio [OR]: 1.474, P = .047), central depression or ulceration in the lesion (OR: 1.474, P = .013), previous endoscopic mucosal resection (EMR) or polypectomy procedure (OR: 2.428, P = .020) were associated with technically difficult ESD. Descending colon-located tumor (OR: 5.355, P < .001), and use of IT knife (OR: 4.157, P = .003) were associated with perforation. Recognizing factors associated with technically difficult ESD can help in planning the ESD procedure beforehand.

Cytological Features of Fibrin-associated Diffuse Large B-cell Lymphoma Arising in Retroperitoneal Pseudocyst: The First Case Report.

BACKGROUND/AIM: Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is frequently associated with the Epstein-Barr virus (EBV) and manifests as non-mass-forming microscopic lesions within fibrin-rich lesions. Herein, we describe the cytological features of FA-DLBCL. CASE REPORT: A 72-year-old man presented with a large retroperitoneal cystic mass that was treated by cyst aspiration and laparoscopic excision. Individually dispersed large, atypical cells in a necrotic background contained scant cytoplasm and hyperchromatic nuclei with irregular nuclear contours, frequent karyorrhectic debris, and mitotic figures. A fibrinous exudate with necrotic material attached to the inner surface of the cystic mass contained large, atypical cells that were individually scattered or arranged in small clusters. These were positive for cluster of differentiation 20 and Epstein-Barr virus-encoded RNA in situ hybridization. CONCLUSION: We cytologically characterized FA-DLBCL as large, atypical cells that were individually scattered or arranged in small clusters in a necrotic background. To the best of our knowledge, we revealed the cytological features of FA-DLBCL.

Comparison of Clinicopathological and Prognostic Characteristics Between Minimal Deviation Adenocarcinoma and Gastric-type Endocervical Adenocarcinoma.

BACKGROUND/AIM: Minimal deviation adenocarcinoma (MDA) is an extremely well-differentiated variant of gastric-type endocervical adenocarcinoma (GEA). This study compared the clinicopathological and prognostic characteristics of MDA to those of GEA. PATIENTS AND METHODS: Nine MDAs and 22 GEAs were included in this study. We reviewed electronic medical records and pathology slides to collect clinicopathological and prognostic information. RESULTS: GEA showed significantly higher stage at presentation, more frequent parametrial extension and lymphovascular space invasion, and recurrence than MDA. Patients with GEA had significantly lower survival rates than those with MDA. None of the cases with MDA exhibited singly dispersed or clustered tumor cells, diffuse stromal desmoplasia, severe nuclear pleomorphism, loss of nuclear polarity, or coarse chromatin, all of which were frequently observed in GEA. CONCLUSION: Significant differences were observed in the clinicopathological characteristics and patient outcomes between MDA and GEA. Further investigations using a larger cohort are warranted to determine the clinical behavior and aggressiveness of MDA.

Selenoprotein W engages in overactive osteoclast differentiation in multiple myeloma.

BACKGROUND: Patients with multiple myeloma exhibit malignant osteolytic bone disease due to excessive osteoclast formation and function. We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function. METHODS AND RESULTS: We observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNFα), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNFα was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-κB and NFATc1, which are favorable for osteoclast formation. CONCLUSION: Our findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma.

Time interval of esomeprazole and dual antiplatelet therapy in patients with cardiocerebrovascular diseases.

Dual antiplatelet therapy (DAPT) with the combination of clopidogrel and aspirin is recommended for preventing secondary ischemic events in patients with acute coronary syndrome (ACS) or acute ischemic stroke (AIS). Proton pump inhibitors (PPIs) are suggested as preventive treatment for these patients. Due to clopidogrel-PPI interactions, separating their administration might be considered. However, a paucity of studies has been conducted to investigate the outcome differences between concurrent and interval-based use in ACS and AIS patients. Our study aimed to evaluate clinical outcomes based on administration timing. This study included patients with ACS or AIS onset or recurrence of within the last month. Patients who were expected to receive DAPT for at least 6 months and who were currently taking or planning to take esomeprazole were included. Patients were divided into Group 1 (interval administration group, IA group) and Group 2 (concurrent administration group, CA group) according to the interval between esomeprazole and DAPT administration. The time interval was based on 12 hours. The primary outcome was the occurrence of major adverse cardiocerebrovascular events (MACCEs), and safety outcomes were defined as major bleeding, minor bleeding and gastrointestinal bleeding and intracranial hemorrhage. A total of 3600 patients completed this study. The proportions of patients in the 2 groups were as follows: CA group, 99% (n = 3489) and IA group, 1% (n = 111). The primary outcome occurred in 0.9% of patients in the IA group and 1.8% of patients in the CA group (P = .51). There was no significant distinction in the overall bleeding risk of the CA group compared to that of the IA group (2.75% in the CA group and 2.70% in the IA group). Additionally, there was no significant difference observed between the 2 groups for safety outcomes. This multicenter, prospective, observational study that enrolled patients with ACS or AIS demonstrated that there was no significant difference in the occurrence of MACCEs and bleeding issues within 6 months according to the medication administration interval. The majority of patients with DAPT were taking PPIs simultaneously in real-world practice.