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1.
Am J Gastroenterol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38976448

RESUMO

INTRODUCTION: Zastaprazan is a potent potassium-competitive acid blocker (P-CAB) developed to treat gastroesophageal reflux disease. This study aims to evaluate the efficacy and safety of zastaprazan compared to esomeprazole in patient with erosive esophagitis (EE). METHODS: A phase III, multicenter, randomized, double-blind, non-inferiority clinical study was conducted with 300 subjects with confirmed EE. Subjects were randomized to receive zastaprazan 20 mg or esomeprazole 40 mg once daily up to 8 weeks. The primary endpoint was the cumulative proportion of subject with healed EE confirmed by endoscopy at week 8. The secondary endpoints included the healing rate at week 4, symptom response and quality of life assessment. Safety profiles and serum gastrin levels were also assessed. RESULTS: In the full analysis set, the cumulative healing rate at week 8 were 97.92% (141/144) for zastaprazan and 94.93% (131/138) (P = 0.178) for esomeprazole. The healing rate at week 4 in the zastaprazan group was higher than esomeprazole group (95.14% (137/144) vs. 87.68% (121/138); P = 0.026). There was no significant difference between groups in healing rates (the per-protocol set) at week 8 and week 4, symptom responses, quality of life assessments and safety profiles. In addition, serum gastrin levels increased during treatment in both groups, with a significant difference between the two groups (P = 0.047), but both decreased after treatment. DISCUSSION: An 8-week therapy of zastaprazan 20 mg is non-inferior to esomeprazole 40 mg in subjects with predominantly low-grade EE. The healing rate at week 4 appears to be higher for zastaprazan than esomeprazole.

2.
Diagnostics (Basel) ; 14(13)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39001348

RESUMO

Colorectal neoplasms are prevalent in patients with chronic kidney disease (CKD); however, the safety and efficacy of colorectal endoscopic submucosal dissection (ESD) are not well understood. This retrospective analysis included ESD procedures performed in 1266 patients with CKD across five tertiary medical institutions from January 2015 to December 2020. Patients were categorized based on their estimated glomerular filtration rate (eGFR), which ranged from CKD1 to CKD5 (including those on dialysis). We found that en bloc resection rates remained high across all CKD stages, affirming the procedural efficacy of ESD. Notably, the prevalence of cardiovascular comorbidities, such as ischemic heart disease and diabetes mellitus, significantly increased with an advancing CKD stage, with a corresponding increase in the Charlson Comorbidity Index, highlighting the complexity of managing these patients. Despite these challenges, the complete resection rate was lower in the CKD5 group (50%) than in the CKD1 group (83.4%); however, procedural complications, such as perforation and bleeding, did not significantly differ among the groups. The predictive models for complete resection and major complications showed no significant changes with a decreasing eGFR. These findings underscore that ESD is a feasible and safe treatment for colorectal neoplasms in patients with CKD, successfully balancing the inherent procedural risks with clinical benefits.

3.
J Clin Med ; 13(13)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38999497

RESUMO

Background and Objectives: Colorectal endoscopic submucosal dissection (ESD) is an effective technique for removing colorectal neoplasms with large or cancerous lesions. However, there are few studies on post-ESD electrocoagulation syndrome (PECS), a complication of colorectal ESD. Therefore, this study aimed to investigate the various risk factors for PECS after colorectal ESD. Materials and Methods: We retrospectively analyzed the medical records of 1413 lesions from 1408 patients who underwent colorectal ESD at five tertiary hospitals between January 2015 and December 2020. We investigated the incidence and risk factors associated with PECS. Based on the data, we developed a risk-scoring model to predict the risk of PECS after colorectal ESD. Results: The incidence rate of PECS was 2.6% (37 patients). In multivariate analysis, the use of anti-platelet agents (odds ratio (OR), 2.474; 95% confidence interval (CI), 1.088-5.626; p < 0.031), a lesion larger than 6 cm (OR 3.755; 95% CI, 1.237-11.395; p = 0.028), a deep submucosal invasion (OR 2.579; 95% CI, 1.022-6.507; p = 0.045), and an ESD procedure time ≥ 60 min (OR 2.691; 95% CI, 1.302-5.560; p = 0.008) were independent risk factors of PECS after colorectal ESD. We developed a scoring model for predicting PECS using these four factors. As the score increased, the incidence of PECS also increased, from 1.3% to 16.6%. PECS occurred more frequently in the high-risk group (≥2) (1.8% vs. 12.4%, p < 0.001). Conclusions: In this study, the risk factors for PECS after colorectal ESD were the use of anti-platelet agents, a lesion larger than 6 cm, a deep submucosal invasion, and an ESD procedure time ≥ 60 min. The risk-scoring model developed in this study using these factors could be effective in predicting and preventing PECS.

4.
J Gynecol Oncol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39028151

RESUMO

OBJECTIVE: In this study, we evaluated the role of prolonged progestin treatment on atypical endometrial hyperplasia (AEH) patients who did not achieve complete regression (CR) after at least 3 months of progestin treatment. Possible prognostic factors predicting disease regression and recurrence were also assessed. METHODS: We retrospectively identified patients who had histologically confirmed persistent disease after at least 3 months of progestin treatment at two tertiary centers in Korea and Taiwan. Clinicopathologic factors and clinical outcomes were obtained from medical records. Logistic regression was used to analyze the relationship between covariates and the probability of CR and relapse. RESULTS: Fifty-two patients were included. Thirty-seven of 52 patients (71.2%) achieved CR after prolonged progestin treatment. Median time from starting progestin treatment to CR was 12.0 months. Daily administration of medroxyprogesterone acetate ≥200 mg or megestrol acetate ≥80 mg was associated with higher probability of regression. Nineteen of 37 patients (51.4%) experienced recurrence, with median time from CR to relapse of 15.0 months. Body mass index ≥27 was associated with higher relapse probability. Twelve of 16 patients with disease progression to endometrial carcinoma underwent surgery. The 12 cases had stage I tumors and lived without disease. CONCLUSION: Extension of progestin treatment course is feasible for AEH patients without an initial response to progestin. Higher daily progestin dosage was associated with higher probability of CR, and obesity was associated with higher risk of relapse. The patients without an initial response to progestins and whose AEH progressed to endometrial carcinoma had good prognoses.

5.
Viruses ; 16(6)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38932128

RESUMO

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.


Assuntos
Enterovirus Humano A , Regiões Promotoras Genéticas , Enterovirus Humano A/genética , Enterovirus Humano A/fisiologia , Animais , Proteínas Virais/genética , Proteínas Virais/metabolismo , Humanos , Doença de Mão, Pé e Boca/virologia , Linhagem Celular , Células Sf9 , Vetores Genéticos/genética
6.
In Vivo ; 38(4): 2009-2015, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38936946

RESUMO

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.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Masculino , Ressecção Endoscópica de Mucosa/métodos , Feminino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Colonoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tempo de Internação , Adulto
7.
In Vivo ; 38(4): 1973-1983, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38936897

RESUMO

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.


Assuntos
Carcinoma Endometrioide , Neoplasias Ovarianas , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/virologia , Adulto , Diagnóstico Diferencial , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/terapia , Adenocarcinoma Mucinoso/secundário , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Idoso , Adenocarcinoma/virologia , Adenocarcinoma/secundário , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Papillomaviridae/isolamento & purificação , Metástase Neoplásica , Papillomavirus Humano
8.
Digestion ; : 1-11, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865978

RESUMO

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.

9.
J Korean Med Sci ; 39(24): e191, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38915283

RESUMO

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.


Assuntos
Anticoagulantes , Fibrilação Atrial , Inibidores da Agregação Plaquetária , Humanos , Fibrilação Atrial/tratamento farmacológico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Anticoagulantes/uso terapêutico , Quimioterapia Combinada , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Fibrinolíticos/uso terapêutico , Infarto do Miocárdio , Hemorragia , Revascularização Miocárdica , Modelos de Riscos Proporcionais , Pontuação de Propensão , Incidência , República da Coreia
10.
Sensors (Basel) ; 24(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38894258

RESUMO

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.


Assuntos
Indústria da Construção , Fadiga , Humanos , Fadiga/fisiopatologia , Adulto , Masculino , Equilíbrio Postural/fisiologia , Dispositivos Eletrônicos Vestíveis , Acidentes por Quedas/prevenção & controle
11.
Artigo em Inglês | MEDLINE | ID: mdl-38852582

RESUMO

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.

12.
Anticancer Res ; 44(6): 2605-2616, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38821623

RESUMO

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.


Assuntos
Neoplasias da Mama , Perfilação da Expressão Gênica , Transcriptoma , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Pessoa de Meia-Idade , Adulto , Fatores Etários , Regulação Neoplásica da Expressão Gênica , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Idoso
13.
Nat Commun ; 15(1): 4253, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762636

RESUMO

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.


Assuntos
Cistadenocarcinoma Seroso , Aprendizado Profundo , Neoplasias Ovarianas , Platina , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/genética , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/diagnóstico por imagem , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/genética , Platina/uso terapêutico , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Resultado do Tratamento , Gradação de Tumores , Estudos de Coortes , Adulto , Reprodutibilidade dos Testes
14.
Expert Rev Proteomics ; 21(5-6): 237-246, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38697802

RESUMO

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.


Assuntos
Biomarcadores , Humanos , Biomarcadores/análise , Proteômica/métodos , Programas de Rastreamento/métodos , Ensaios de Triagem em Larga Escala/métodos
15.
J Am Heart Assoc ; 13(10): e033611, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38761083

RESUMO

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.


Assuntos
Aspirina , Clopidogrel , Terapia Antiplaquetária Dupla , AVC Isquêmico , Inibidores da Agregação Plaquetária , Sistema de Registros , Humanos , Clopidogrel/uso terapêutico , Aspirina/uso terapêutico , Masculino , Idoso , Feminino , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/mortalidade , AVC Isquêmico/diagnóstico , AVC Isquêmico/prevenção & controle , Terapia Antiplaquetária Dupla/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Pessoa de Meia-Idade , Resultado do Tratamento , Idoso de 80 Anos ou mais , Fatores de Tempo , Japão/epidemiologia , Prevenção Secundária/métodos , Prevenção Secundária/tendências , Quimioterapia Combinada , Fatores de Risco
16.
Gut Pathog ; 16(1): 26, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715101

RESUMO

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.

17.
Sci Rep ; 14(1): 12353, 2024 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811758

RESUMO

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.


Assuntos
Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Margens de Excisão , Recidiva Local de Neoplasia , Humanos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Masculino , Feminino , Ressecção Endoscópica de Mucosa/métodos , Idoso , Recidiva Local de Neoplasia/patologia , Pessoa de Meia-Idade , Neoplasia Residual/patologia , Resultado do Tratamento , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Metástase Linfática
18.
Anticancer Res ; 44(5): 2159-2170, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38677751

RESUMO

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.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Biomarcadores Tumorais , Proteínas de Ligação a DNA , Imuno-Histoquímica , Neoplasias Pulmonares , Fator de Transcrição PAX8 , Feminino , Humanos , Masculino , Adenocarcinoma/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/secundário , Biomarcadores Tumorais/metabolismo , Diagnóstico Diferencial , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Fator de Transcrição PAX8/metabolismo , Fator Nuclear 1 de Tireoide/metabolismo , Fatores de Transcrição/metabolismo
19.
Anticancer Res ; 44(5): 2193-2204, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38677732

RESUMO

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.


Assuntos
Adenocarcinoma , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Pessoa de Meia-Idade , Prognóstico , Adulto , Idoso , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade
20.
In Vivo ; 38(3): 1477-1482, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688594

RESUMO

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.


Assuntos
Cistos , Fibrina , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Idoso , Linfoma Difuso de Grandes Células B/patologia , Fibrina/metabolismo , Cistos/patologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Neoplasias Retroperitoneais/patologia , Tomografia Computadorizada por Raios X
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