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1.
BMC Musculoskelet Disord ; 25(1): 379, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745277

RESUMO

BACKGROUND: Biomarkers that predict the treatment response in patients with knee osteoarthritis are scarce. This study aimed to investigate the potential role of synovial fluid cell counts and their ratios as biomarkers of primary knee osteoarthritis. METHODS: This retrospective study investigated 96 consecutive knee osteoarthritis patients with knee effusion who underwent joint fluid aspiration analysis and received concomitant intra-articular corticosteroid injections and blood tests. The monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) were calculated. After 6 months of treatment, patients were divided into two groups: the responder group showing symptom resolution, defined by a visual analog scale (VAS) score of ≤ 3, without additional treatment, and the non-responder group showing residual symptoms, defined by a VAS score of > 3 and requiring further intervention, such as additional medication, repeated injections, or surgical treatment. Unpaired t-tests and univariate and multivariate logistic regression analyses were conducted between the two groups to predict treatment response after conservative treatment. The predictive value was calculated using the area under the receiver operating characteristic curve, and the optimal cutoff value was determined. RESULTS: Synovial fluid MLR was significantly higher in the non-responder group compared to the responder group (1.86 ± 1.64 vs. 1.11 ± 1.37, respectively; p = 0.02). After accounting for confounding variables, odds ratio of non-responder due to increased MLR were 1.63 (95% confidence interval: 1.11-2.39). The optimal MLR cutoff value for predicting patient response to conservative treatment was 0.941. CONCLUSIONS: MLR may be a potential biomarker for predicting the response to conservative treatment in patients with primary knee osteoarthritis.


Assuntos
Tratamento Conservador , Linfócitos , Monócitos , Osteoartrite do Joelho , Líquido Sinovial , Humanos , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Líquido Sinovial/citologia , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Tratamento Conservador/métodos , Injeções Intra-Articulares , Biomarcadores/análise , Biomarcadores/sangue , Valor Preditivo dos Testes , Contagem de Leucócitos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38798239

RESUMO

Background: The diagnostic accuracy of preoperative radiologic findings in predicting the tumor characteristics and clinical outcomes of papillary thyroid microcarcinoma (PTMC) was evaluated across all risk groups. Methods: In total, 939 PTMC patients, comprising both low-risk and non-low-risk groups, who underwent surgery were enrolled. The preoperative tumor size and lymph node metastasis (LNM) were evaluated by ultrasonography within 6 months before surgery and compared with the postoperative pathologic findings. Discrepancies between the preoperative and postoperative tumor sizes were analyzed, and clinical outcomes were assessed. Results: The agreement rate between radiological and pathological tumor size was approximately 60%. Significant discrepancies were noted, including an increase in tumor size in 24.3% of cases. Notably, in 10.8% of patients, the postoperative tumor size exceeded 1 cm, despite being initially classified as 0.5 to 1.0 cm based on preoperative imaging. A postoperative tumor size >1 cm was associated with aggressive pathologic factors such as multiplicity, microscopic extrathyroidal extension, and LNM, as well as a higher risk of distant metastasis. In 30.1% of patients, LNM was diagnosed after surgery despite not being suspected before the procedure. This group was characterized by smaller metastatic foci and lower risks of distant metastasis or recurrence than patients with LNM detected both before and after surgery. Conclusion: Among all risk groups of PTMCs, a subset showed an increase in tumor size, reaching 1 cm after surgery. These cases require special consideration due to their association with adverse clinical outcomes, including an elevated risk of distant metastasis.

4.
Gut Liver ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38715439

RESUMO

Background/Aims: : Endoscopic papillectomy (EP) is increasingly used as an alternative to surgery for managing benign ampullary neoplasms. However, post-EP resection margins are often positive or indeterminate, and there is no consensus on the management of ampullary adenomas with positive or indeterminate margins after EP. This study was designed to compare the long-term outcomes between resected margin-negative (RMN) and resected margin-positive/indeterminate (RMPI) groups and to identify factors associated with clinical outcomes. Methods: : This retrospective analysis included patients with ampullary adenoma without evidence of adenocarcinoma who underwent EP between 2004 and 2016. The RMN and RMPI groups were compared for recurrence rates and recurrence-free duration during a mean follow-up duration of 71.7±39.8 months. Factors related to clinical outcomes were identified using multivariate analysis. Results: : Of the 129 patients who underwent EP, 82 were in the RMN group and 47 were in the RMPI group. The RMPI group exhibited a higher recurrence rate compared to the RMN group (14.6% vs 34.0%, p=0.019). However, the recurrence-free duration was not significantly different between the groups (34.7±32.6 months vs 36.2±27.4 months, p=0.900). Endoscopic treatment successfully managed recurrence in both groups (75% vs 75%). Submucosal injection was a significant risk factor for residual lesions (hazard ratio, 4.11; p=0.009) and recurrence (hazard ratio, 2.57; p=0.021). Conclusions: : Although ampullary adenomas with positive or indeterminate margins after EP showed a higher rate of recurrence at long-term follow-up, endoscopic treatment was effective with favorable long-term outcomes. Submucosal injection prior to resection was associated with increased risk of recurrence and residual lesions.

5.
Heliyon ; 10(7): e28474, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560227

RESUMO

Deciding on a career and securing employment at an ideal company represent significant challenges for students. Employment is not only a personal achievement but also a measure of success for universities and governments. To transform students into competitive applicants, various activities are provided by universities, governments, and companies. These activities may leave students either excited about the prospects or overwhelmed by the experience. The aim of this study is to explore the relationship between college experiences and post-graduation employment through an analysis of a five-year activity log. Specifically, students' diverse activities were categorized into six core competencies: skill reinforcement, leadership and teamwork, globalization, organizational commitment, job exploration, and autonomous implementation. We used logistic regression to examine how these competencies relate to employment status, and ANOVA analysis to assess their impact on initial salaries. The findings reveal that while competencies in skill improvement, job exploration, and organizational commitment were not statistically significant, those in leadership and teamwork, globalization, and autonomous implementation were crucial for securing employment. Additionally, globalization, job exploration, and autonomous implementation competencies influenced annual salary levels. Furthermore, a comparison of students completing either a single major or a convergent major revealed that job exploration competency significantly impacts the annual salary level.

6.
Cancer Res Treat ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38637967

RESUMO

Purpose: Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors (ICIs), presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential. Materials and Methods: We explored the molecular characteristics of CD8+ T cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis. Results: In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T (MAIT) cell and NKT cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The IFN-γ signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer. Conclusion: Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.

7.
Cancer Res Treat ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605661

RESUMO

Purpose: Hereditary diffuse gastric cancer (HDGC) presents a significant genetic predisposition, notably linked to mutations in the CDH1 and CTNNA1. However, the genetic basis for over half of HDGC cases remains unidentified. The aim of this study is to identify novel pathogenic variants in HDGC and evaluate their protein expression. Materials and Methods: Among 20 qualifying families, two were selected based on available pedigree and DNA. Whole genome sequencing (WGS) on DNA extracted from blood and whole exome sequencing (WES) on DNA from formalin-fixed paraffin-embedded tissues were performed to find potential pathogenic variants in HDGC. After selection of a candidate variant, functional validation and enrichment analysis were performed. Results: As a result of WGS, three candidate germline mutations (EPHA5, MCOA2, and RHOA) were identified in one family. After literature review and in silico analyses, the RHOA mutation (R129W) was selected as a candidate. This mutation was found in two gastric cancer patients within the family. In functional validation, it showed RhoA overexpression and a higher GTP-bound state in the RhoaR129W mutant. Decreased phosphorylation at Ser127/397 suggested altered YAP1 regulation in the Rho-ROCK pathway. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses linked RhoAR129W overexpression to changed migration/adhesion in MKN1 cell line. However, this RHOA mutation (R129W) was not found in index patients in other families. Conclusion: The RHOA mutation (R129W) emerges as a potential causative gene for HDGC, but only in one family, indicating a need for further studies to understand its role in HDGC pathogenesis fully.

8.
Sci Rep ; 14(1): 7806, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565880

RESUMO

The rapid proliferation and integration of AI chatbots in office environments, specifically the advanced AI model ChatGPT, prompts an examination of how its features and updates impact knowledge processes, satisfaction, and word-of-mouth (WOM) among office workers. This study investigates the determinants of WOM among office workers who are users of ChatGPT. We adopted a quantitative approach, utilizing a stratified random sampling technique to collect data from a diverse group of office workers experienced in using ChatGPT. The hypotheses were rigorously tested through Structural Equation Modeling (SEM) using the SmartPLS 4. The results revealed that system updates, memorability, and non-language barrier attributes of ChatGPT significantly enhanced knowledge acquisition and application. Additionally, the human-like personality traits of ChatGPT significantly increased both utilitarian value and satisfaction. Furthermore, the study showed that knowledge acquisition and application led to a significant increase in utilitarian value and satisfaction, which subsequently increased WOM. Age had a positive influence on WOM, while gender had no significant impact. The findings provide theoretical contributions by expanding our understanding of AI chatbots' role in knowledge processes, satisfaction, and WOM, particularly among office workers.


Assuntos
Boca , Condições de Trabalho , Humanos , Face , Teoria Ética , Conhecimento
9.
Biomolecules ; 14(4)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38672468

RESUMO

So Shiho Tang (SSHT) is a traditional herbal medicine commonly used in Asian countries. This study evaluated the anti-inflammatory effect of SSHT and the associated mechanism using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and murine dextran sodium sulfate (DSS)-induced ulcerative colitis models. Pre-treatment of RAW 264.7 macrophages with SSHT significantly reduced LPS-induced inflammation by decreasing nitrite production and regulating the mitogen-activated protein kinase pathway. Meanwhile, in mice, DSS-induced colitis symptoms, including colon shortening and body weight loss, were attenuated by SSHT. Moreover, representative compounds of SSHT, including glycyrrhizic acid, ginsenoside Rb1, baicalin, saikosaponin A, and saikosaponin B2, were quantified, and their effects on nitrite production were measured. A potential anti-inflammatory effect was detected in LPS-induced RAW 264.7 cells. Our findings suggest that SSHT is a promising anti-inflammatory agent. Its representative components, including saikosaponin B2, ginsenoside Rb1, and baicalin, may represent the key active compounds responsible for eliciting the anti-inflammatory effects and can, therefore, serve as quality control markers in SSHT preparations.


Assuntos
Anti-Inflamatórios , Sulfato de Dextrana , Lipopolissacarídeos , Macrófagos , Animais , Camundongos , Lipopolissacarídeos/farmacologia , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/patologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/patologia , Masculino , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacologia
10.
Foods ; 13(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38472902

RESUMO

This study investigated the impact of Methyl Jasmonate (MeJA) application on the nutritional content and yield of five different colored radish microgreens. Microgreens were produced without substrate and subjected to 0.5 mM and 1.0 mM MeJA treatments on the 7th day, three days before harvest. The parameters measured included yield, dry matter, minerals, amino acids, secondary metabolites such as chlorophylls (Chls), anthocyanins, flavonoids, phenolics, glucosinolates (GSLs), vitamin C, and antioxidant capacity. MeJA at 1.0 mM generally improved yield and dry weight across cultivars, and all microgreens exhibited rich mineral and amino acid composition, with the influence of cultivar being more significant than MeJA treatment. However, MeJA enhanced all cultivars' anthocyanins, GSLs, phenolics, flavonoids, and antioxidant activities. Generally, as the antioxidant capacity is the primary factor influencing the nutritional quality of microgreens, MeJA-treated microgreens, especially with selected superior cultivars such as 'Asia purple' and 'Koregon red', could offer a potential for cultivation of value-added, eco-friendly microgreens with substrate-free cultivation.

11.
Proc Natl Acad Sci U S A ; 121(14): e2400868121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38547066

RESUMO

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.


Assuntos
Bexiga Urinária , Infecções Urinárias , Animais , Humanos , Bexiga Urinária/cirurgia , Urodinâmica/fisiologia , Próteses e Implantes , Cistectomia
12.
Plants (Basel) ; 13(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38475455

RESUMO

Aruncus spp. has been used as a traditional folk medicine worldwide for its anti-inflammatory, hemostatic, and detoxifying properties. The well-known species A. dioicus var. kamtschaticus has long been used for multifunctional purposes in Eastern Asia. Recently, it was reported that its extract has antioxidant and anti-diabetic effects. In this respect, it is likely that other Aruncus spp. possess various biological activities; however, little research has been conducted thus far. The present study aims to biologically identify active compounds against diabetes in the Korean endemic plant A. aethusifolius and evaluate the underlying mechanisms. A. aethusifolius extract enhanced glucose uptake without toxicity to C2C12 cells. A bioassay-guided isolation of A. aethusifolius yielded two pure compounds, and their structures were characterized as glycolipid derivatives, gingerglycolipid A, and (2S)-3-linolenoylglycerol-O-ß-d-galactopyranoside by an interpretation of nuclear magnetic resonance and high-resolution mass spectrometric data. Both compounds showed glucose uptake activity, and both compounds increased the phosphorylation levels of insulin receptor substrate 1 (IRS-1) and 5'-AMP-activated protein kinase (AMPK) and protein expression of peroxisome proliferator-activated receptor γ (PPARγ). Gingerglycolipid A docked computationally into the active site of IRS-1, AMPK1, AMPK2, and PPARγ (-5.8, -6.9, -6.8, and -6.8 kcal/mol).

13.
Ann Surg Oncol ; 31(6): 3694-3704, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38530528

RESUMO

BACKGROUND: Vascularized gastroepiploic lymph node transfer (VGLNT) is a well-accepted surgical treatment for restoring physiological function in chronic lymphedema. However, the inclusion of substantial lymph nodes (LNs) in the flap remains uncertain. This study aimed to identify the anatomical basis for reliable flap harvest for VGLNT. PATIENTS AND METHODS: The anatomy of perigastric station 4d LNs was studied in healthy cadavers (n = 15) and patients with early gastric cancer (EGC) (n = 27). The omentum was divided into three segments: proximal, middle, and distal from the origin of the right gastroepiploic vessels. The flap dimension, number, location, size of LNs, and caliber of the vessels were reviewed. Eight patients underwent VGLNT for upper/lower limb lymphedema. RESULTS: The mean numbers of LNs in the proximal, middle, and distal segment were 2.5, 1.4, 0.5 in the cadavers, and 4.9, 2.7, 0.7 in the gastrectomy specimens, respectively. The proximal third included a significantly greater number of LNs than the distal third in the cadaveric (p = 0.024) and ECG (p = 0.016) specimens. A total of 95% of the LNs were located within proximal two-thirds of the flap from the vessel origin both in the cadavers (21.0 × 5.0 cm) and in the gastrectomy specimens (20 × 3.5 cm). In VGLNT, the transferred flap was 25.5 ± 6.9 × 4.1 + 0.7 cm in dimension, containing a mean number of 6.5 ± 1.9 LNs. At postoperative 6 months, the volumetric difference was significantly reduced by 22.8 ± 9.2% (p < 0.001). CONCLUSIONS: This study provides a distinct distribution pattern of station 4d LNs. Inclusion of the proximal two-thirds of the flap, which carries majority of the LNs, is recommended for VGLNT.


Assuntos
Cadáver , Gastrectomia , Linfonodos , Linfedema , Neoplasias Gástricas , Retalhos Cirúrgicos , Humanos , Linfonodos/cirurgia , Linfonodos/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Gastrectomia/métodos , Linfedema/cirurgia , Idoso , Artéria Gastroepiploica/cirurgia , Adulto , Prognóstico , Estudos de Casos e Controles , Seguimentos
14.
Surg Obes Relat Dis ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38418337

RESUMO

BACKGROUND: Obesity is known to increase overall disease burden but does obesity management actually help reduce disease burden? OBJECTIVES: To investigate the effects of weight loss on disease burden in people with obesity using the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in Korea. SETTING: Pure longitudinal observational study using Nationwide cohort database. METHODS: Out of 514,866 NHIS-HEALS cohort, participants with class II obesity in Asia-Pacific region (30 ≤ body mass index [BMI] < 35) who underwent health check-up provided by NHIS during 2003-2004 (index date) were included. All final participants continued to receive a total of 5 biennial health check-ups over the next 10 years without missing. A group-based trajectory model (GBTM) was used to categorize subjects based on 10-year BMI change patterns. The changes of co-morbidities, healthcare resource utilization, and medical cost were analyzed. RESULTS: The final study subjects (9857) were categorized into 3 trajectory clusters based on the pattern of BMI (kg/m2) change: maintenance (57.35%) with an average change of -.02 ± .06, loss (38.65%) with -.04 ± .08, and substantial loss (4.0%) with -.10 ± .18. The annual increases in the number of co-morbidities per subject in each cluster were .18, .18, and .16 (all P < .001), respectively. The increase of healthcare resource utilization over time was lowest for the substantial loss compared to maintenance and loss. With each passing year, the average annual total healthcare cost increased by ₩21,200 ($16.48, P = .034) and ₩10,500 ($8.16, P = .498) in the maintenance and loss, respectively, but decreased by ₩62,500 ($48.59, P = .032) in the substantial loss. CONCLUSIONS: Weight loss in people with obesity was associated with a reduced burden of disease, as evidenced by lower co-morbidity, healthcare resource utilization rate, and decreased medical costs. This study highlights the potential positive long-term impact on Korean society when actively managing weight in individuals with obesity.

15.
J Appl Gerontol ; : 7334648241236081, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38410030

RESUMO

This pilot study explored whether a socially assistive robot (SAR) would have positive effects on Korean American immigrant older adults' health behaviors and emotional well-being and whether the older adults would be receptive to the SAR. A total of 30 participants (age 65+) in a large metropolitan area participated in the study, and each participant was provided a SAR named Hyodol for 4 months and interacted with it in ways that they saw appropriate. We used one-group pre- and post-test design to assess changes between baseline and follow-up in medication adherence, depressive symptoms, loneliness, and disability. Additionally, we employed in-depth qualitative interviews to explore participants' perceptions about the SAR. At post-test, participants showed improved medication adherence, reduced depressive symptoms, and a slightly and statistically nonsignificant decrease in loneliness scores. Qualitative data suggested high adoptability of this particular SAR among the participants.

16.
Cancer ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376914

RESUMO

BACKGROUND: Telomere length is associated with cancer risk and cancer aggressiveness. Radioactive iodine (RAI) therapy for thyroid cancer has raised concerns for second primary malignancy (SPM) in patients with high cumulative doses. The association between RAI dose and peripheral blood leukocyte telomere length was examined. METHODS: A total of 425 patients were included who underwent total thyroidectomy and were followed up for at least 1 year with or without RAI treatment. The relative telomere length (RTL) of the patients was assessed via a quantitative polymerase chain reaction amplification method. RAI doses were divided into five groups on the basis of cumulative dose, and a comparison was made among these groups. RESULTS: The number of patients with RAI treatment was 287 (67.5%), and the cumulative RAI dose was 3.33 GBq (range, 1.11-131.35 GBq). The mean RTL was significantly shorter in the highest RAI group (>22.2 GBq) compared to both the no-RAI and lower dose groups. The association between RAI dose and RTL was positive in the lower RAI group (1.1-3.7 GBq) and negative in the highest RAI group in both univariate and multivariate analyses. We observed 59 (13.9%) SPMs and 20 (4.7%) mortalities, and RTL did not show a significant risk effect for all-cause, thyroid cancer-specific, or SPM-specific mortality. CONCLUSIONS: In patients with thyroid cancer who underwent total thyroidectomy, peripheral blood leukocyte telomere length exhibited a significant association with cumulative RAI dose higher than 22.2 GBq. These results suggest the possibility of telomere length shortening in patients who undergo high-dose RAI treatment.

17.
Pancreatology ; 24(3): 424-430, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38395676

RESUMO

BACKGROUND: Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX. METHODS: Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed. RESULTS: With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy. CONCLUSIONS: The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gencitabina , Estudos Retrospectivos , Adenocarcinoma/patologia , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Terapia Neoadjuvante , Progressão da Doença , Irinotecano , Oxaliplatina
18.
Ann Surg Oncol ; 31(5): 3024-3030, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38372863

RESUMO

BACKGROUND: This study aimed to investigate the oncologic long-term safety of proximal gastrectomy for upper-third advanced gastric cancer (AGC) and Siewert type II esophagogastric junction (EGJ) cancer. METHODS: The study enrolled patients who underwent proximal gastrectomy (PG) or total gastrectomy (TG) with standard lymph node (LN) dissection for pathologically proven upper-third AGC and EGJ cancers between January 2007 and December 2018. Propensity score-matching with a 1:1 ratio was performed to reduce the influence of confounding variables such as age, sex, tumor size, T stage, N stage, and tumor-node-metastasis (TNM) stage. Kaplan-Meier survival analysis was performed to analyze oncologic outcome. The prognostic factors of recurrence-free survival (RFS) were analyzed using the Cox proportional hazard analysis. RESULTS: Of the 713 enrolled patients in this study, 60 received PG and 653 received TG. Propensity score-matching yielded 60 patients for each group. The overall survival rates were 61.7 % in the PG group and 68.3 % in the TG group (p = 0.676). The RFS was 86.7 % in the PG group and 83.3 % in the TG group (p = 0.634). The PG group showed eight recurrences (1 anastomosis site, 1 paraaortic LN, 1 liver, 1 spleen, 1 lung, 1 splenic hilar LN, and 2 remnant stomachs). In the multivariate analysis, the operation method was not identified as a prognostic factor of tumor recurrence. CONCLUSION: The patients who underwent PG had a long-term oncologic outcome similar to that for the patients who underwent TG for upper-third AGC and EGJ cancer.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Adenocarcinoma/patologia , Recidiva Local de Neoplasia/patologia , Gastrectomia , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Neoplasias Gástricas/patologia , Resultado do Tratamento
19.
Tissue Eng Regen Med ; 21(3): 487-497, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38294592

RESUMO

BACKGROUND: Currently, there is no apparent treatment for sarcopenia, which is characterized by diminished myoblast function. We aimed to manufacture exosomes that retain the myogenic differentiation capacity of human fetal cartilage-derived progenitor cells (hFCPCs) and investigate their muscle regenerative efficacy in myoblasts and a sarcopenia rat model. METHODS: The muscle regeneration potential of exosomes (F-Exo) secreted during myogenic differentiation of hFCPCs was compared to human bone marrow mesenchymal stem cells-derived (hBMSCs) exosomes (B-Exo) in myoblasts and sarcopenia rat model. The effect of F-Exo was analyzed through known microRNAs (miRNAs) analysis. The mechanism of action of F-Exo was confirmed by measuring the expression of proteins involved in the Wnt signaling pathway. RESULTS: F-Exo and B-Exo showed similar exosome characteristics. However, F-Exo induced the expression of muscle markers (MyoD, MyoG, and MyHC) and myotube formation in myoblasts more effectively than B-Exo. Moreover, F-Exo induced greater increases in muscle fiber cross-sectional area and muscle mass compared to B-Exo in a sarcopenia rat. The miR-145-5p, relevant to muscle regeneration, was found in high concentrations in the F-Exo, and RNase pretreatment reduced the efficacy of exosomes. The effects of F-Exo on the expression of myogenic markers in myoblasts were paralleled by the miR-145-5p mimics, while the inhibitor partially negated this effect. F-Exo was involved in the Wnt signaling pathway by enhancing the expression of Wnt5a and ß-catenin. CONCLUSION: F-Exo improved muscle regeneration by activating the Wnt signaling pathway via abundant miR-145-5p, mimicking the remarkable myogenic differentiation potential of hFCPCs.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Sarcopenia , Humanos , Ratos , Animais , Exossomos/metabolismo , Sarcopenia/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Músculo Esquelético/metabolismo , Cartilagem/metabolismo
20.
Gastric Cancer ; 27(2): 221-234, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38212543

RESUMO

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.


Assuntos
Carcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Feminino , Humanos , Masculino , Neoplasias Gástricas/patologia , Herpesvirus Humano 4 , Prognóstico , Carcinoma/complicações
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