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1.
J Am Heart Assoc ; 13(8): e032771, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38606761

RESUMO

BACKGROUND: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. METHODS AND RESULTS: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05). CONCLUSIONS: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.


Assuntos
Doenças Cardiovasculares , Hipertensão , Hipotensão , Idoso , Feminino , Humanos , Masculino , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco de Doenças Cardíacas , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/complicações , Fatores de Risco
3.
Med Biol Eng Comput ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38575823

RESUMO

Accurately predicting the prognosis of ischemic stroke patients after discharge is crucial for physicians to plan for long-term health care. Although previous studies have demonstrated that machine learning (ML) shows reasonably accurate stroke outcome predictions with limited datasets, to identify specific clinical features associated with prognosis changes after stroke that could aid physicians and patients in devising improved recovery care plans have been challenging. This study aimed to overcome these gaps by utilizing a large national stroke registry database to assess various prediction models that estimate how patients' prognosis changes over time with associated clinical factors. To properly evaluate the best predictive approaches currently available and avoid prejudice, this study employed three different prognosis prediction models including a statistical logistic regression model, commonly used clinical-based scores, and a latest high-performance ML-based XGBoost model. The study revealed that the XGBoost model outperformed other two traditional models, achieving an AUROC of 0.929 in predicting the prognosis changes of stroke patients followed for 3 months. In addition, the XGBoost model maintained remarkably high precision even when using only selected 20 most relevant clinical features compared to full clinical datasets used in the study. These selected features closely correlated with significant changes in clinical outcomes for stroke patients and showed to be effective for predicting prognosis changes after discharge, allowing physicians to make optimal decisions regarding their patients' recovery.

4.
Front Microbiol ; 15: 1337570, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38525074

RESUMO

Background: Meropenem belongs to the carbapenem class, which is categorized as beta-lactam antibiotics. These antibiotics are administered in intermittent bolus doses at specific time intervals. However, the continuous infusion approach ensures sustained drug exposure, maintaining the drug concentration above the minimum inhibitory concentration (MIC) throughout the entire treatment period. This study aimed to find out the association between continuous infusions of meropenem and mortality rates. Materials and methods: We conducted a search of the PubMed/Medline, EMBASE, Cochrane Central, and ClinicalTrials.gov databases up to 14 August 2023. The six randomized controlled trials (RCTs) were identified and included in our analysis. The random-effects model was implemented using Comprehensive Meta-Analysis software to examine the outcomes. Results: Our study included a total of 1,529 adult patients from six randomized controlled trials. The primary outcome indicated that continuous infusion of meropenem did not lead to reduction in the mortality rate (odds ratio = 0.844, 95% CI: 0.671-1.061, P =0.147). Secondary outcomes revealed no significant differences in ICU length of stay (LOS), ICU mortality, clinical cure, or adverse events between continuous infusion and traditional intermittent bolus strategies of meropenem. Notably, we observed significant improvements in bacterial eradication (odds ratio 19 = 2.207, 95% CI: 1.467-3.320, P < 0.001) with continuous infusion of meropenem. Our study also suggested that performing continuous infusion may lead to better bacterial eradication effects in resistant pathogens (coefficient: 2.5175, P = 0.0138*). Conclusion: Continuous infusion of meropenem did not result in the reduction of mortality rates but showed potential in improving bacterial eradication. Furthermore, this strategy may be particularly beneficial for achieving better bacterial eradication, especially in cases involving resistant pathogens.

5.
PLoS One ; 19(3): e0300173, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547184

RESUMO

Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Terapia Neoadjuvante/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamento farmacológico , Estadiamento de Neoplasias , Prognóstico , Linfonodos/patologia , Quimiorradioterapia/métodos , Estudos Retrospectivos , Esofagectomia/métodos
6.
Helicobacter ; 29(1): e13033, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37950342

RESUMO

BACKGROUND: The eradication rates of sequential therapy are high in clinical trials; however, the adherence for follow-up or the patient population in a real-world setting might be different from those in trails. This study investigates the effectiveness of sequential therapy in a real-world setting and the factors that lead to treatment failure. MATERIALS AND METHODS: In this retrospective study, patients receiving sequential therapy as a first-line anti-Helicobacter pylori (H. pylori) treatment in a real-world setting were reviewed. The age adjusted Charlson Comorbidity Index (age-CCI) and baseline variety of medications were reviewed to determine factors correlated with nonadherence for post-treatment testing and H. pylori eradication failure. RESULTS: A total of 1053 patients were reviewed. A total of 579 patients receiving sequential therapy were included in the analyses. Among them, 462 received post-treatment testing and were placed into the follow-up group. Thus, the post-treatment testing rate was 79.8%. Stroke was an independent factor of nonadherence for post-treatment testing. In the follow-up group, the eradication failure rate was 8.2%. Female sex (odds ratio [OR] 2.41 [95% CI 1.16-5.03], p = 0.02) and age-CCI ≥2 (OR 3.16 [1.05-9.48], p = 0.04) were independent factors of H. pylori eradication failure. The eradication failure rates were 14.4%, 7.8%, 7.1%, and 3.1% for the females with age-CCI ≥2, females with age-CCI <2, males with age-CCI ≥2, and males with age-CCI <2 subgroups, respectively (p = 0.027). CONCLUSIONS: In a real-world setting, the adherence rate of post-treatment testing for sequential therapy as a first-line anti-H. pylori treatment was found to be suboptimal. Female sex and age-CCI ≥2 were independent factors of eradication failure.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Masculino , Humanos , Feminino , Antibacterianos , Infecções por Helicobacter/tratamento farmacológico , Estudos Retrospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Quimioterapia Combinada , Fatores de Risco , Resultado do Tratamento , Claritromicina/uso terapêutico , Amoxicilina
7.
J Clin Med ; 12(24)2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38137586

RESUMO

Background: The efficacy of remdesivir in reducing disease severity among COVID-19-infected patients has been established, but concerns have emerged regarding the potential side effects of bradycardia. The aim of this study was to investigate the association between remdesivir-induced bradycardia and mortality, while also identifying the related risk factors. Materials and methods: The PubMed/Medline, Cochrane Central and ClinicalTrials.gov databases were searched. Randomized controlled trials and prospective or retrospective cohort studies were included (through 14 July 2023). The random-effects model was implemented using Comprehensive Meta-Analysis software version 3.0 to examine the outcomes. Results: A total of 12 prospective or retrospective studies involving 7674 patients were analyzed. The primary outcomes revealed a significant association between remdesivir administration and bradycardia development (Odds ratio = 2.556, 95% CI = 2.049-3.188, p < 0.001). However, no statistically significant increase in the mortality rate was observed among patients with bradycardia during remdesivir treatment (Odds ratio = 0.872, 95% CI = 0.483-1.576, p = 0.651). The secondary outcome demonstrated a significant association between chronic kidney disease (CKD) and remdesivir-induced bradycardia (OR: 1.251, 95% CI: 1.003-1.561, p = 0.047). Moreover, patients with obesity (OR = 1.347, 95% CI = 1.098-1.652, p = 0.004) were more likely to experience remdesivir-induced bradycardia. Conclusions: Although a higher risk of bradycardia occurred during remdesivir treatment, the occurrence of remdesivir-induced bradycardia did not lead to higher mortality. Our study also identified patients with obesity and CKD as high-risk subgroups for experiencing bradycardia during remdesivir treatment.

8.
FASEB J ; 37(10): e23181, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37668436

RESUMO

NEDDylation is a type of protein post-translational modification that has high similarity to ubiquitination. UBE1C encodes NEDDylation E1 enzyme, locates at chromatin region 3p14.1 and shows high gene dosage amplification frequency in both Asian and Caucasian lung cancer patients. However, its NEDDylation substrates and roles in tumorigenesis remain elucidated. In this study, we aim to investigate the oncogenic role of UBE1C and its involvement in how NEDDylation regulates p53 in lung cancer. We found that UBE1C mRNA overexpression and DNA amplification in most of the lung cell lines and cancer patients. Patients with UBE1C overexpression showed poor prognosis. Moreover, we demonstrated that overexpression of UBE1C and NEDD8, a NEDDylation moiety, resulted in the p53 NEDDylation with inhibition of p53 acetylation at K373 residue. Importantly, UBE1C-mediated NEDDylation downregulated the transcriptional activity of p53 by inhibiting p53 ability to target promoter regions of its downstream transcription targets, consequently inhibiting the promoter activities and the expression of mRNA and protein of the p53 downstream genes including p21 and PTEN. In addition, UBE1C and NEDD8 overexpression promoted migration, invasion, and proliferation of lung cancer cells. Our findings suggest that UBE1C acts as an oncogene with prognostic potential and highlight a potential role of UBE1C-mediated NEDDylation in downregulation of p53 transcriptional activity in lung cancer.


Assuntos
Neoplasias Pulmonares , Proteína Supressora de Tumor p53 , Enzimas Ativadoras de Ubiquitina , Humanos , Acetilação , Carcinogênese , Neoplasias Pulmonares/genética , Oncogenes , Proteína Supressora de Tumor p53/genética , Enzimas Ativadoras de Ubiquitina/genética
9.
Thorac Cancer ; 14(28): 2821-2829, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37675608

RESUMO

Esophageal squamous cell carcinoma (ESCC) exhibits high incidence with poor prognosis. Alcohol drinking, cigarette smoking, and betel nut chewing are well-known risk factors. Dysbiosis, an imbalance of the microbiota residing in a local environment, is known to be associated with human diseases, especially cancer. This article reviews the current evidence of esophageal microbiota in ESCC carcinogenesis, including initiation, progression, and drug resistance. Articles involving the esophageal microbiota, diagnosis, treatment, and the progression of esophageal cancer were acquired using a comprehensive literature search in PubMed in recent 10 years. Based on 16S rRNA sequencing of human samples, cell, and animal studies, current evidence suggests dysbiosis of the esophagus promotes ESCC progression and chemotherapy resistance, leading to a poor prognosis. Smoking and drinking are associated with esophageal dysbiosis. Specific bacteria have been reported to promote carcinogenesis, involving either progression or drug resistance in ESCC, for example Porphyromonas gingivalis and Fusobacterium nucleatum. These bacteria promote ESCC cell proliferation and migration via the TLR4/NF-κB and IL-6/STAT3 pathways. F. nucleatum induces cisplatin resistance via the enrichment of immunosuppressive myeloid-derived suppressor cells (MDSCs). Correcting the dysbiosis and reducing the abundance of specific esophageal pathogens may help in suppressing cancer progression. In conclusion, esophageal dysbiosis is associated with ESCC progression and chemoresistance. Screening the oral and esophageal microbiota is a potential diagnostic tool for predicting ESCC development or drug-resistance. Repairing esophageal dysbiosis is a novel treatment for ESCC. Clinical trials with probiotics in addition to current chemotherapy are warranted to study the therapeutic effects.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Microbiota , Animais , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Disbiose/complicações , RNA Ribossômico 16S , Carcinogênese
10.
Nutrients ; 15(14)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37513689

RESUMO

Lipid-lowering drugs (LLDs) have protective effects against coronary artery disease (CAD) and cerebrovascular disease (CVD); however, a paradoxical association with cholesterol has been identified in several diseases, such as diabetes, dementia, and atrial fibrillation. We aimed to analyze the association between LLDs and cholesterol levels in older adults with type 2 diabetes mellitus (T2DM). This cross-sectional study enrolled consecutive patients aged ≥50 years from three centers in Taiwan. A multiple logistic regression model was used, and odds ratios (ORs) for different levels of total cholesterol (TC) or low-density-lipoprotein cholesterol (LDL-C) compared with the highest level were adjusted for age, triglyceride level, sex, comorbidities, and medications. Among the 3688 participants, 572 with and 676 without T2DM used LLDs. After adjusting for age and sex, the non-T2DM group demonstrated better medical conditions, cognition, and daily function than the T2DM group, regardless of LLD use. Compared to the highest TC level (≥240 mg/dL), ORs were significantly increased as TC levels decreased. A similar pattern of T2DM prevalence was observed in LDL-C levels. Older people with T2DM demonstrated low cognitive and daily functions. Significantly reduced TC and LDL levels were associated with a higher T2DM prevalence in older adults regardless of LLD use. T2DM was associated with impaired cognitive and daily functioning. A higher prevalence of T2DM in older people with low cholesterol levels raises doubt surrounding cognition and daily function being jeopardized when the "lower is better" strategy is applied for the secondary prevention of CAD or CVD.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Humanos , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Transversais , LDL-Colesterol , Fatores de Risco , Colesterol , Hipolipemiantes/uso terapêutico , Doença da Artéria Coronariana/complicações , Estudos de Coortes , HDL-Colesterol , Triglicerídeos
11.
Gastrointest Endosc ; 98(5): 755-764, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37356632

RESUMO

BACKGROUND AND AIMS: Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis. METHODS: This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy. RESULTS: Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded. CONCLUSIONS: The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).

12.
World Neurosurg ; 175: 142-150, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37169077

RESUMO

BACKGROUND: Cervical spondylotic myelopathy (CSM) may seriously affect quality of life. In the literature, there is scarce evidence of the pros and cons of full endoscopic spine surgery in the treatment of CSM. The main purpose of this study was to conduct a systematic review to elucidate the efficacy of full endoscopic spine surgery in the management of patients with CSM. METHODS: This systematic review was conducted in accordance with the PRISMA guidelines. A systematic search of Web of Science, PubMed MEDLINE, Embase, and Cochrane Library was conducted from the database inception to February 1, 2023. RESULTS: The study included 183 patients and their age was 56.78 ± 7.87 years. The average surgical time calculated was 96.34 ± 33.58 minutes. Intraoperative blood loss ranged from a minimal amount to 51 mL. The average duration of hospital stay was 3.56 ± 1.6 days. The average span for follow-up was on an interval of 18.7 ± 6.76 months. Significant improvements were noted in all aspects of functional outcomes and image results after full endoscopic cervical spine surgery, with no major complications. CONCLUSIONS: The current study found that both anterior transcorporeal and posterior surgical approaches could be used for the treatment of CSM with a full endoscopic technique. Indications of full endoscopic cervical spine surgery for CSM included cervical disc herniation, central canal stenosis, calcified ligamentum flavum, and ossification of the posterior longitudinal ligament. Improved postoperative outcomes with acceptable surgical complications were noted in this systematic review.


Assuntos
Doenças da Medula Espinal , Espondilose , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Espondilose/cirurgia , Espondilose/complicações , Resultado do Tratamento , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/complicações , Vértebras Cervicais/cirurgia , Descompressão Cirúrgica/métodos
13.
J Clin Hypertens (Greenwich) ; 25(3): 266-274, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36748892

RESUMO

The present study investigated the prognostic values for office brachial (OB), office central (OC), and ambulatory daytime brachial (AmDB) hypertension, as defined by a unifying threshold of 130/80 mmHg, and the incremental value of either OC or AmDB hypertension to OB hypertension. A total of 1219 community residents without receiving anti-hypertensive treatment (671 men and 548 women, aged ≥ 30 years old) from central Taiwan and Kinmen islands had OB, OC, and AmDB blood pressure measurements during a cardiovascular survey conducted in 1992-1993. OB hypertension, OC hypertension, and AmDB hypertension were all defined in retrospect at the threshold of 130/80 mmHg. They were followed up for nonfatal and fatal cardiovascular events until December 31, 2017, by linking the baseline database to the National Health Insurance Research dataset and the National Death Registry. During a follow-up of 25 612.5 person-years (Average event-free time: 21.0 years), there were 368 fatal and nonfatal cardiovascular events. In multivariable analyses, OB hypertension, OC hypertension, and AmDB hypertension had similar hazard ratios for cardiovascular events [2.03, 95% confidence interval: 1.47-2.80]; 1.92 (1.47-2.51); and 1.79 (1.41-2.29), respectively. Using OB normotension as the reference, either the concordant OB and OC hypertension [2.24 (1.61-3.12)], or the concordant OB and AmDB hypertension [2.52 (1.80-3.54)] was significantly associated with cardiovascular events. Moreover, OB hypertension plus AmDB normotension was also significantly associated with increased risk for cardiovascular events. We concluded that OB hypertension, OC hypertension, and AmDB hypertension defined by a unifying threshold of 130/80 mmHg may provide similar estimates of long-term risk for cardiovascular events. Cross-classification analyses suggest that addition of OC hypertension or AmDB hypertension may improve the prognostic value of OB hypertension.


Assuntos
Doenças Cardiovasculares , Hipertensão , Masculino , Humanos , Feminino , Adulto , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/etiologia , Monitorização Ambulatorial da Pressão Arterial/métodos , Anti-Hipertensivos/uso terapêutico
14.
PLoS One ; 18(1): e0269096, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36701340

RESUMO

OBJECTIVE: This study evaluated short-term (1-month) and long-term (1-year) mortality risks associated with the glomerular filtration rate (eGFR) on admission for patients with intracerebral hemorrhage. METHODS: From the Taiwan Stroke Registry data from April 2006 to December 2016, we identified and stratified patients with intracerebral hemorrhage into five subgroups by the eGFR level on admission: ≥90, 60-89, 30-59, 15-29, and <15 mL/min/1.73 m2 or on dialysis. Risks for 1-month and 1-year mortality after intracerebral hemorrhage were compared by the eGFR levels. RESULTS: Both the 1-month and 1-year mortality rates progressively increased with the decrease in eGFR levels. The 1-month mortality rate in patients with eGFR < 15 mL/min/1.73 m2 or on dialysis was approximately 5.5-fold greater than that in patients with eGFR ≥ 90 mL/min/1.73 m2 (8.31 versus 1.50 per 1000 person-days), with an adjusted hazard ratio (HR) of 4.59 [95% confidence interval (CI) = 2.71-7.78]. Similarly, the 1-year mortality in patients with eGFR < 15 mL/min/1.73 m2 or on dialysis was 7.5 times that in patients with eGFR ≥ 90 mL/min/1.73 m2 (2.34 versus 0.31 per 1000 person-days), with an adjusted HR of 4.54 (95% CI 2.95-6.98). CONCLUSION: Impairment of renal function is an independent risk factor for mortality in patients with intracerebral hemorrhage in a gradual way. The eGFR level is a prognostic indicator for patients with intracerebral hemorrhage.


Assuntos
Diálise Renal , Acidente Vascular Cerebral , Humanos , Hemorragia Cerebral , Fatores de Risco , Taxa de Filtração Glomerular , Rim/fisiologia
15.
Gastrointest Endosc ; 97(6): 1083-1091.e1, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36720289

RESUMO

BACKGROUND AND AIMS: The red material occupying the larger portion of the acquired sample in EUS fine-needle biopsy (FNB) is seldom investigated. We aimed to evaluate the composition of the red material. METHODS: Patients with a solid pancreatic mass who received EUS FNB from September 2020 to June 2021 were enrolled. The white or yellowish content with apparent bulk (white material) and the rest of pasta-like red content (red material) were separated immediately after puncture. Needle passes proceeded until 2 specimens with >4 mm of white material were obtained. An extra needle pass was conducted for DNA collection. The DNA amount, Kirsten rat sarcoma virus (K-ras) mutation type, and mutation allele frequency were compared between the white and red material. RESULTS: Forty patients were enrolled with 68 paired white and red materials. The diagnostic accuracy was slightly higher in the white material (92.5% vs 82.5%, P = .219). On the histology slides, the area of the tumor gland was comparable in both materials, but the total tissue area was larger in the red material (9.74 mm2 and 10.74 mm2 larger according to generalized linear model and generalized estimating equation, respectively; both, P < .001). The amount of DNA was significantly higher in the red material (2.99 [interquartile range, 1.59-7.29] µg vs .70 [interquartile range, .27-1.24] µg; P < .001). Common pancreatic adenocarcinoma K-ras mutation was identified at a rate of 85% for the white material and 95% for the red material. Regardless of whether red or white material was used, there was a high concordance of K-ras mutation types (34 of 40 [85%]) and a high correlation of mutation allele frequency (ρ = .66, P < .001). CONCLUSIONS: In EUS FNB, the red material contains a higher amount of tumor DNA and can be an alternative source for tumor DNA analysis.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas
16.
Mol Carcinog ; 62(2): 277-287, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36342355

RESUMO

Esophageal squamous cell carcinoma (ESCC) is highly resistant to chemoradiation therapy. We aimed to examine whether Nutlin-3, a molecule that suppresses murine double min 2 (MDM2)-mediated p53 and Retinoblastoma (RB) protein degradation leading to downregulation of DNA methyltransferases (DNMTs), can be a novel therapeutic agent for ESCC. We used wild-type and chemoradiation-resistant ESCC cell lines in this study. The expression of DNMTs, p53 and RB, and methylation level of tumor suppressor genes (TSG) were analyzed upon Nutlin-3 treatment. The antitumor efficacy of Nutlin-3 was investigated in ESCC cell lines and xenograft tumor model. TSG protein expression was checked in the excised tumor tissue. Nutlin-3 induced upregulation of p53 and RB and downregulation of DNMTs proteins in the chemoradiation-resistant and aggressive ESCC cells. The methylation level of TSGs was decreased by Nutlin-3. Nutlin-3 inhibits clonogenic growth of ESCC cells and exerts a synergistic cytotoxic-effect when combined with chemotherapeutic agent cisplatin. Moreover, xenograft tumor growth in SCID mice was suppressed by Nutlin-3. The protein expression level of DNMTs was downregulated, and that of TSGs was upregulated by Nutlin-3 treatment in the excised tumor tissue. In conclusion, Nutlin-3 is a potential therapeutic agent that can potentiate the treatment efficacy of chemoradiation-resistant ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Animais , Humanos , Camundongos , Apoptose , Linhagem Celular Tumoral , DNA/farmacologia , Inibidores Enzimáticos/farmacologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/radioterapia , Metiltransferases/metabolismo , Metiltransferases/farmacologia , Camundongos SCID , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína do Retinoblastoma/metabolismo , Proteína Supressora de Tumor p53/genética
17.
J Formos Med Assoc ; 122(5): 400-410, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36463082

RESUMO

BACKGROUND: This study is aimed toward investigating the evolution of each Correa's step after Helicobacter pylori eradication in a long-term follow-up and exploring the factors correlated with a high-risk of gastric cancer. METHODS: A total of 1824 H. pylori-infected subjects were enrolled to receive screening endoscopy. Among them, 491 received surveillance endoscopy. The patients were divided into Correa's steps I to VI, from normal to gastric cancer. A group-based trajectory model was used to classify patients as persistent high-risk status or not. RESULTS: The prevalence rates of positive corpus-predominant gastritis index (CGI) were 20%-40% in all age groups and Correa's steps IV-V increased >35% after 50 years based on screening endoscopy. Successful eradication of H. pylori regressed CGI after the 1st year-and-thereafter (P < 0.05) and decreased Correa's step progression (Relative risk 0.66 [95% CI 0.49-0.89], P = 0.01); however, it did not regress OLGA and OLGIM. Not only in steps IV-V, but also in step III, the patients had a risk of developing gastric cancer (11.13-76.41 and 4.61 per 1000 person-years). Age (Hazard ratio 1.012 [1.003-1.020], P = 0.01), OLGA stages ≥ I (2.127 [1.558-2.903], P < 0.001), and OLGIM stages ≥ I (1.409 [1.119-1.774], P = 0.004) were correlated independently with a persistent high-risk status. CONCLUSION: The patients in Correa's steps III-V, but not I-II, were at risk of gastric cancer after H. pylori eradication. Age, OLGA stages ≥ I, and OLGIM stages ≥ I were independent factors correlated to a persistent high-risk of gastric cancer. The data may be useful when scheduling surveillance endoscopy for subjects in each Correa's step (NCT04527055).


Assuntos
Dispepsia , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Úlcera Gástrica , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Gastrite/epidemiologia , Endoscopia Gastrointestinal , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Mucosa Gástrica
18.
Gut Liver ; 17(2): 318-327, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36052613

RESUMO

Background/Aims: A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses. Methods: A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed. Results: A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman̕s ρ=0.568). Conclusions: Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).


Assuntos
Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Estudos Cross-Over , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Sucção/métodos , Estudos Prospectivos , Pâncreas/diagnóstico por imagem
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