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3.
Ann Surg Oncol ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39283578

RESUMEN

BACKGROUND: Performing laparoscopic surgery for T4 colon cancer remains controversial because of concerns about whether its oncologic outcomes are comparable to those of open surgery, and postoperative peritoneal metastasis (PM) has been reported to occur more frequently in laparoscopic colectomy for T4 colon cancer. We investigated whether minimally invasive surgery (MIS) demonstrated a higher PM rate than open surgery and analyzed the risk factors for PM in pT4 colon cancer. METHODS: This study included 392 patients with pT4 colon cancer who underwent curative surgery at a referral hospital between January 2000 and December 2018. Patients with previous neoadjuvant therapy, synchronous malignancy, metastasis, or those who underwent hyperthermic intraperitoneal chemotherapy were excluded. RESULTS: The MIS group had fewer high-risk clinical features, such as tumors too large for endoscope admission or complications like perforation and fistula. The group also exhibited shorter operative time, intraoperative blood loss, multivisceral resection, hospital stay, fewer postoperative complications, smaller tumor size, lower pT4b ratio, and higher pN+ rates. Multivariate analysis revealed that high-risk clinical features, MIS, pT4b, pN+, tumor size < 5 cm, high histological grade, lymphovascular invasion, and postoperative complications were significant risk factors for PM. During the median 59-month follow-up, the 5-year cumulative incidence of PM was elevated in the MIS group (17.5% vs. 8.2%; P = 0.057). No significant differences were observed in the 5-year overall and disease-free survival rates. CONCLUSIONS: Minimally invasive surgery increases the risk of postoperative PM in patients with pT4 colon cancer. Surgeons may require thorough tumor staging and radical resection to prevent PM.

4.
J Ginseng Res ; 48(4): 347-353, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39036728

RESUMEN

Ginsenosides in ginseng are known for their potential health benefits, including antioxidant properties and their potential to exhibit anticancer effects. Besides a various range of coding genes, ginsenosides impose their efficacy by targeting noncoding RNAs. Long noncoding RNA ( lncRNA) has gained significant attention from both basic and clinical oncology fields due to its involvement in various cancer cell activities such as proliferation, apoptosis, metastasis, and autophagy. These events can be achieved either by lncRNA alone or in association with microRNAs or proteins. This review aims to summarize the diverse activities of lncRNAs that are regulated by ginsenosides, focusing on their role in regulating target genes through signaling pathways in human diseases. We highlight the results of studies on the expression profiles of lncRNAs induced by ginsenosides in efforts to inhibit cancer cell proliferation. Finally, we discuss the potential and challenges of utilizing lncRNAs as diagnostic markers for disease treatment.

5.
Front Public Health ; 12: 1359127, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38846620

RESUMEN

Introduction: Individuals with gender dysphoria do not identify with their sex assigned at birth and face societal and cultural challenges, leading to increased risk for depression, anxiety, and suicide. Gender dysphoria is a DSM-5 diagnosis but is not necessary for transition therapy. Additionally, individuals with gender dysphoria or who identify as gender diverse/nonconforming may experience "minority stress" from increased discrimination, leading to a greater risk for mental health problems. This study aimed to identify possible health disparities in patients hospitalized for depression with gender dysphoria across the United States. Depression was selected because patients with gender dysphoria are at an increased risk for it. Various patient and hospital-related factors are explored for their association with changes in healthcare utilization for patients hospitalized with depression. Methods: The National Inpatient Sample was used to identify nationwide patients with depression (n = 378,552, weighted n = 1,892,760) from 2016 to 2019. We then examined the characteristics of the study sample and investigated how individuals' gender dysphoria was associated with healthcare utilization measured by hospital cost per stay. Multivariate survey regression models were used to identify predictors. Results: Among the 1,892,760 total depression inpatient samples, 14,145 (0.7%) patients had gender dysphoria (per ICD-10 codes). Over the study periods, depression inpatients with gender dysphoria increased, but total depression inpatient rates remained stable. Survey regression results suggested that gender dysphoria, minority ethnicity or race, female sex assigned at birth, older ages, and specific hospital regions were associated with higher hospital cost per stay than their reference groups. Sub-group analysis showed that the trend was similar in most racial and regional groups. Conclusion: Differences in hospital cost per stay for depression inpatients with gender dysphoria exemplify how this community has been disproportionally affected by racial and regional biases, insurance denials, and economic disadvantages. Financial concerns can stop individuals from accessing gender-affirming care and risk more significant mental health problems. Increased complexity and comorbidity are associated with hospital cost per stay and add to the cycle.


Asunto(s)
Depresión , Disforia de Género , Humanos , Estados Unidos , Femenino , Masculino , Disforia de Género/terapia , Adulto , Persona de Mediana Edad , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Costos de Hospital/estadística & datos numéricos , Anciano , Adolescente , Adulto Joven , Tiempo de Internación/estadística & datos numéricos , Tiempo de Internación/economía
6.
Nucl Med Mol Imaging ; 58(4): 237-245, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38932755

RESUMEN

Positron emission tomography/computed tomography (PET/CT) has dramatically altered the landscape of noninvasive glioma evaluation, offering complementary insights to those gained through magnetic resonance imaging (MRI). PET/CT scans enable a multifaceted analysis of glioma biology, supporting clinical applications from grading and differential diagnosis to mapping the full extent of tumors and planning subsequent treatments and evaluations. With a broad array of specialized radiotracers, researchers and clinicians can now probe various biological characteristics of gliomas, such as glucose utilization, cellular proliferation, oxygen deficiency, amino acid trafficking, and reactive astrogliosis. This review aims to provide a recent update on the application of versatile PET/CT radiotracers in glioma research and clinical practice.

7.
Front Immunol ; 15: 1362858, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38545102

RESUMEN

Background: Cardiac arrest (CA) is a significant public health concern. There is the high imminent mortality and survival in those who are resuscitated is substantively compromised by the post-CA syndrome (PCAS), characterized by multiorgan ischemia-reperfusion injury (IRI). The inflammatory response in PCAS is complex and involves various immune cell types, including lymphocytes and myeloid cells that have been shown to exacerbate organ IRI, such as myocardial infarction. Purinergic signaling, as regulated by CD39 and CD73, has emerged as centrally important in the context of organ-specific IRI. Hence, comprehensive understanding of such purinergic responses may be likewise imperative for improving outcomes in PCAS. Methods: We have investigated alterations of immune cell populations after CA by utilizing rodent models of PCAS. Blood and spleen were collected after CA and resuscitation and underwent flow cytometry analysis to evaluate shifts in CD3+CD4+ helper T cells, CD3+CD8a+ cytotoxic T cells, and CD4/CD8a ratios. We then examined the expression of CD39 and CD73 across diverse cell types, including myeloid cells, T lymphocytes, and B lymphocytes. Results: In both rat and mouse models, there were significant increases in the frequency of CD3+CD4+ T lymphocytes in PCAS (rat, P < 0.01; mouse, P < 0.001), with consequently elevated CD4/CD8a ratios in whole blood (both, P < 0.001). Moreover, CD39 and CD73 expression on blood leukocytes were markedly increased (rat, P < 0.05; mouse, P < 0.01 at 24h). Further analysis in the experimental mouse model revealed that CD11b+ myeloid cells, with significant increase in their population (P < 0.01), had high level of CD39 (88.80 ± 2.05 %) and increased expression of CD73 (P < 0.05). CD19+ B lymphocytes showed slight increases of CD39 (P < 0.05 at 2h) and CD73 (P < 0.05 at 2h), while, CD3+ T lymphocytes had decreased levels of them. These findings suggested a distinct patterns of expression of CD39 and CD73 in these specific immune cell populations after CA. Conclusions: These data have provided comprehensive insights into the immune response after CA, highlighting high-level expressions of CD39 and CD73 in myeloid cells.


Asunto(s)
Paro Cardíaco , Roedores , Animales , Ratones , Ratas , Citometría de Flujo , Leucocitos , Linfocitos T Citotóxicos , 5'-Nucleotidasa/metabolismo
8.
Chronic Illn ; : 17423953241241759, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38532693

RESUMEN

OBJECTIVE: The clinical aspects of lung cancer patients are well-studied. However, healthcare charge patterns have yet to be explored through a large-scale representative population-based sample investigating differences by socioeconomic factors and comorbidities. AIM: To identify how comorbidities associated with healthcare charges among lung cancer patients. METHODS: We examined the characteristics of the patient sample and the association between comorbidity status (diabetes, hypertension, or both) and healthcare charge. Multivariate survey linear regression models were used to estimate the association. We also investigated sub-group association through various patient and socioeconomic factors. RESULTS: Of 212,745 lung cancer patients, 68.5% had diabetes and/or hypertension. Hospital charges were higher in the population with comorbidities. The results showed that lung cancer patients with comorbidities had 9.4%, 5.1%, and 12.0% (with diabetes, hypertension, and both, respectively) higher hospital charges than those without comorbidities. In sub-group analysis, Black patients also showed a similar trend across socioeconomic (i.e. household income and primary payer) and racial (i.e. White, Black, Hispanic, and Asian/Pacific Islander) factors. DISCUSSION: Black patients may be significantly financially burdened because of the prevalence of comorbidities and low-income status. More work is required to ensure healthcare equality and promote access to care for the uninsured, low-income, and minority populations because comorbidities common in these populations can create more significant financial barriers.

9.
Eur J Nucl Med Mol Imaging ; 51(6): 1763-1772, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38200396

RESUMEN

PURPOSE: [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limitations in prostate cancer (PCa) detection owing to low glycolysis in the primary tumour. Recently, prostate-specific membrane antigen (PSMA) PET/CT has been useful for biochemical failure detection and radioligand therapy (RLT) guidance. However, few studies have evaluated its use in primary prostate tumours using PSMA and [18F]FDG PET/CT. This study aimed to evaluate [18F]PSMA-1007 and [18F]FDG PET/CT for primary tumour detection and understand the association of metabolic heterogeneity with clinicopathological characteristics at staging and postoperatively. METHOD: This prospective study included 42 index tumours (27 acinar and 15 ductal-dominant) in 42 patients who underwent [18F]PSMA-1007 and [18F]FDG PET/CT and subsequent radical prostatectomy. All patients were followed for a median of 26 mo, and serum prostate-specific antigen levels were measured every 3 mo to evaluate biochemical failure. One-way analysis of variance, Tukey's multiple comparison test, and Fisher's exact test were performed. RESULTS: All 42 index tumours were detected on [18F]PSMA-1007 PET/CT, whereas only 15 were detected on [18F]FDG PET/CT (62.3% vs. 37.7%, p < 0.0001). A high SUVmax for [18F]PSMA-1007 was observed in tumours with high Gleason scores (GS 6-7 vs. GS 8-10; 12.1 vs. 20.1, p < 0.05). Tumours with [18F]FDG uptake were mostly ductal dominant (acinar-dominant 4/27; ductal-dominant; 11/15, p < 0.001), with lower [18F]PSMA-1007 uptake than tumours without [18F]FDG uptake (SUVmax 16.58 vs. 11.19, p < 0.001). There were 16.6% (7/42) of patients with pStage IV in whom the primary tumours were [18F]FDG positive. Biochemical failure was observed in 14.8% (4/27) of patients with [18F]FDG negative tumours but in 53.3% (8/15) of patients with [18F]FDG positive tumours (p = 0.013). CONCLUSIONS: [18F]PSMA-1007 PET/CT was superior to [18F]FDG PET/CT in detecting primary PCa. In contrast, tumours with [18F]FDG uptake are associated with larger size, a ductal-dominant type, and likely to undergo metastasis at staging and biochemical failure postoperatively.


Asunto(s)
Fluorodesoxiglucosa F18 , Estadificación de Neoplasias , Niacinamida/análogos & derivados , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Anciano , Persona de Mediana Edad , Oligopéptidos/química , Estudios Prospectivos , Radiofármacos , Periodo Posoperatorio
10.
Clin Nucl Med ; 49(2): 109-115, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38049976

RESUMEN

PURPOSE: 11 C-acetate (ACE) PET/CT visualizes reactive astrogliosis in tumor microenvironment. This study compared 11 C-ACE and 11 C-methionine (MET) PET/CT for glioma classification and predicting patient survival. PATIENTS AND METHODS: In this prospective study, a total of 142 patients with cerebral gliomas underwent preoperative MRI, 11 C-MET PET/CT, and 11 C-ACE PET/CT. Tumor-to-contralateral cortex (TNR MET ) and tumor-to-choroid plexus ratios (TNR ACE ) were calculated for 11 C-MET and 11 C-ACE. The Kruskal-Wallis test and Bonferroni post hoc analysis were used to compare the differences in 11 C-TNR MET and 11 C-TNR ACE . The Cox proportional hazards regression analysis and classification and regression tree models were used to assess progression-free survival (PFS) and overall survival (OS). RESULTS: The median 11 C-TNR MET and 11 C-TNR ACE for oligodendrogliomas (ODs), IDH1 -mutant astrocytomas, IDH1 -wildtype astrocytomas, and glioblastomas were 2.75, 1.40, 2.30, and 3.70, respectively, and 1.40, 1.20, 1.77, and 2.87, respectively. The median 11 C-TNR MET was significantly different among the groups, except between ODs and IDH1 -wildtype astrocytomas, whereas the median 11 C-TNR ACE was significantly different among all groups. The classification and regression tree model identified 4 risk groups ( IDH1 -mutant with 11 C-TNR ACE ≤ 1.4, IDH1 -mutant with 11 C-TNR ACE > 1.4, IDH1 -wildtype with 11 C-TNR ACE ≤ 1.8, and IDH1 -wildtype with 11 C-TNR ACE > 1.8), with median PFS of 52.7, 44.5, 25.9, and 8.9 months, respectively. Using a 11 C-TNR ACE cutoff of 1.4 for IDH1 -mutant gliomas and a 11 C-TNR ACE cutoff of 2.0 for IDH1 -wildtype gliomas, all gliomas were divided into 4 groups with median OS of 52.7, 46.8, 27.6, and 12.0 months, respectively. Significant differences in PFS and OS were observed among the 4 groups after correcting for multiple comparisons. CONCLUSIONS: 11 C-ACE PET/CT is better for glioma classification and survival prediction than 11 C-MET PET/CT, highlighting its potential role in cerebral glioma patients.


Asunto(s)
Astrocitoma , Neoplasias Encefálicas , Glioma , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Metionina , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Gliosis , Estudios Prospectivos , Glioma/diagnóstico por imagen , Glioma/patología , Racemetionina , Inflamación , Acetatos , Pronóstico , Mutación , Microambiente Tumoral
11.
Ann Rehabil Med ; 48(1): 50-56, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38083839

RESUMEN

OBJECTIVE: To assess the safety and effectiveness of high-density light-emitting diode (LED) irradiation therapy in patients with hand osteoarthritis (OA) and compare the pre- and post-intervention symptoms. METHODS: Twenty-three patients with hand OA underwent eight sessions of high-density LED irradiation therapy directed at the five most painful areas in the finger joints. Each session lasted for 18 minutes; and the sessions were conducted twice a week, for 4 weeks. We evaluated the degree of pain using the visual analogue scale, ring size, and passive range of motion (flexion+extension) for two most painful joints from the baseline to post-therapy (weeks 4 and 6). RESULTS: High-density LED irradiation therapy significantly reduced the pain posttreatment compared with that observed at the baseline (p<0.001). Although improvements were observed in ring size and joint range of motion at 4 and 6 weeks, they were not statistically significant (p>0.05). No adverse events were observed. CONCLUSION: We examined the safety and effectiveness of high-density LED irradiation therapy in reducing pain and hand swelling and improving joint mobility in patients with hand OA. These results suggest that high-density LED irradiation therapy has the potential to be an important strategy for managing hand OA.

12.
J Patient Saf ; 20(3): 164-170, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38126801

RESUMEN

OBJECTIVE: The aim of the study is to identify vulnerable populations at risk of developing decubitus ulcers and their resultant increase in healthcare utilization to promote the use of early prevention methods. METHODS: The National Inpatient Sample of the United States was used to identify hospitalized patients across the country who had a length of stay of 5 or more days (N = 9,757,245, weighted N = 48,786,216) from 2016 to 2020. We examined the characteristics of the entire inpatient sample based on the presence of decubitus ulcers, temporal trends, risk of decubitus ulcer development, and its association with healthcare utilization, measured by discounted hospital charges and length of stay. The multivariate survey logistic regression model was used to identify predictors for decubitus ulcer occurrence, and the survey linear regression model was used to measure how decubitus ulcers are associated with healthcare utilization. RESULTS: Among 48,786,216 nationwide inpatients, 3.9% had decubitus ulcers. The percentage of inpatients with decubitus ulcers who subsequently experienced increased healthcare utilization rose with time. The survey logistic regression results indicate that patients who were Black, older, male, or those reliant on Medicare/Medicaid had a statistically significant increased risk of decubitus ulcers. The survey linear regression results demonstrate that inpatients with decubitus ulcers were associated with increased hospital charges and longer lengths of stay. CONCLUSIONS: Patients with government insurance, those of minority races and ethnicities, and those treated in the Northeast and West may be more vulnerable to pressure ulcers and subsequent increased healthcare utilization. Implementation of early prevention methods in these populations is necessary to minimize the risk of developing decubitus ulcers, even if upfront costs may be increased. For example, larger hospitals were found to have a lower risk of decubitus ulcer development but an increased cost of preventative care. Hence, it is imperative to explore and use universal, targeted preventative methods to improve patient safety.


Asunto(s)
Úlcera por Presión , Humanos , Masculino , Anciano , Estados Unidos/epidemiología , Úlcera por Presión/epidemiología , Úlcera por Presión/prevención & control , Pacientes Internos , Medicare , Hospitales , Aceptación de la Atención de Salud , Tiempo de Internación
13.
J Geriatr Oncol ; 15(2): 101685, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38104479

RESUMEN

INTRODUCTION: Fragmented cancer care, defined as receipt of care from multiple hospitals, has been shown to be associated with poor patient outcomes and high expense. However, evidence regarding the effects of hospital choice by patients with cancer on overall survival are lacking. Thus, we investigated the relationship between patterns of fragmented care and five-year mortality in patients with gastric cancer. MATERIALS AND METHODS: Using the Korean National Health Insurance senior cohort of adults aged ≥60 years, we identified patients with gastric cancer who underwent gastrectomy during 2007-2014. We examined the distribution of the study population by five-year mortality, and used Kaplan-Meier survival curves/log-rank test and Cox proportional hazard model to compare five-year mortality with fragmented cancer care. RESULTS: Among the participants, 19.5% died within five years. There were more deaths among patients who received fragmented care, especially those who transferred to smaller hospitals (46.6%) than to larger ones (40.0%). The likelihood of five-year mortality was higher in patients who received fragmented cancer care upon moving from large to small hospitals than those who did not transfer hospitals (hazard ratio, 1.28; 95% confidence interval, 1.10-1.48, P = .001). Moreover, mortality was higher among patients treated in large hospitals or in the capital area for initial treatment, and this association was greater for patients from rural areas. DISCUSSION: Fragmentation of cancer care was associated with reduced survival, and the risk of mortality was higher among patients who moved from large to small hospitals.


Asunto(s)
Neoplasias Gástricas , Humanos , Anciano , Estudios de Cohortes , Neoplasias Gástricas/terapia , Hospitales , Modelos de Riesgos Proporcionales , República de Corea/epidemiología , Estudios Retrospectivos
14.
Ann Rehabil Med ; 47(6): 483-492, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38053342

RESUMEN

OBJECTIVE: To evaluate the efficacy of light-emitting diode (LED) and their dual-wavelengths as a treatment strategy for osteoarthritis. METHODS: We induced osteoarthritis in male Sprague-Dawley rats by intra-articular injection of sodium iodoacetate into the right rear knee joint. The animals with lesions were divided into an untreated group and an LED-treated group (n=7 each). In the LED-treated group, the lesioned knee was irradiated with lasers (850 and 940 nm) and dose (3.15 J/cm2) for 20 minutes per session, twice a week for 4 weeks. Knee joint tissues were stained and scanned using an in vivo micro-computed tomography (CT) scanner. Serum interleukin (IL)-6 and IL-18 levels were determined using enzyme-linked immuno-sorbent assay. Several functional tests (lines crossed, rotational movement, rearing, and latency to remain rotating rod) were performed 24 hours before LED treatment and at 7, 14, 21, and 28 days after treatment. RESULTS: LED-treated rats showed improved locomotor function and suppressed matrix-degrading cytokines. Micro-CT images indicated that LED therapy had a preserving effect on cartilage and cortical bone. CONCLUSION: LED treatment using wavelengths of 850 and 940 nm resulted in significant functional, anatomical, and histologic improvements without adverse events in a rat model. Further research is required to determine the optimal wavelength, duration, and combination method, which will maximize treatment effectiveness.

15.
Epigenetics ; 18(1): 2276384, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37908128

RESUMEN

Tamoxifen (Tam) has long been a top treatment option for breast cancer patients, but the challenge of eliminating cancer recurrence remains. Here, we identify a signalling pathway involving ELOVL2, ELOVL2-AS1, and miR-1233-3p, which contributes to drug resistance in Tam-resistant (TamR) breast cancer. ELOVL2-AS1, a long noncoding RNA, was significantly upregulated by its antisense gene, ELOVL2, which is known to be downregulated in TamR cells. Additionally, ELOVL2-AS1 underwent the most hypermethylation in MCF-7/TamR cells. Furthermore, patients with breast cancer who developed TamR during chemotherapy had significantly lower expression of ELOVL2-AS1 compared to those who responded to Tam. Ectopic downregulation of ELOVL2-AS1 by siRNA both stimulated cancer cell growth and deteriorated TamR. We also found that ELOVL2-AS1 sponges miR-1233-3p, which has pro-proliferative activity and elevates TamR, leading to the activation of potential target genes, such as MYEF2, NDST1, and PIK3R1. These findings suggest that ELOVL2-AS1, in association with ELOVL2, may contribute to the suppression of drug resistance by sponging miR-1233-3p in breast cancer.


Asunto(s)
Neoplasias de la Mama , MicroARNs , ARN Largo no Codificante , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico , ARN sin Sentido
16.
Proc Natl Acad Sci U S A ; 120(48): e2309780120, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-37983487

RESUMEN

Many autoimmune diseases are characterized by the activation of autoreactive T cells. The T cell repertoire is established in the thymus; it remains uncertain whether the presence of disease-associated autoreactive T cells reflects abnormal T cell selection in the thymus or aberrant T cell activation in the periphery. Here, we describe T cell selection, activation, and T cell repertoire diversity in female mice deficient for B lymphocyte-induced maturation protein (BLIMP)-1 in dendritic cells (DCs) (Prdm1 CKO). These mice exhibit a lupus-like phenotype with an expanded population of T follicular helper (Tfh) cells having a more diverse T cell receptor (TCR) repertoire than wild-type mice and, in turn, develop a lupus-like pathology. To understand the origin of the aberrant Tfh population, we analyzed the TCR repertoire of thymocytes and naive CD4 T cells from Prdm1 CKO mice. We show that early development and selection of T cells in the thymus are not affected. Importantly, however, we observed increased TCR signal strength and increased proliferation of naive T cells cultured in vitro with antigen and BLIMP1-deficient DCs compared to control DCs. Moreover, there was increased diversity in the TCR repertoire in naive CD4+ T cells stimulated in vitro with BLIMP1-deficient DCs. Collectively, our data indicate that lowering the threshold for peripheral T cell activation without altering thymic selection and naive T cell TCR repertoire leads to an expanded repertoire of antigen-activated T cells and impairs peripheral T cell tolerance.


Asunto(s)
Receptores de Antígenos de Linfocitos T , Transducción de Señal , Ratones , Animales , Femenino , Receptores de Antígenos de Linfocitos T/metabolismo , Modelos Animales de Enfermedad , Timo , Antígenos , Linfocitos T Colaboradores-Inductores/metabolismo
17.
Front Immunol ; 14: 1241531, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37744368

RESUMEN

Since the description of age-associated or autoimmune-associated B cells (ABCs), there has been a growing interest in the role of these cells in autoimmunity. ABCs are differently defined depending on the research group and are heterogenous subsets. Here, we sought to characterize ABCs in Sle1/2/3 triple congenic (TC) mice, which is a well accepted mouse model of lupus. Compared to follicular (FO) B cells, ABCs have many distinct functional properties, including antigen presentation. They express key costimulatory molecules for T cell activation and a distinct profile of cytokines. Moreover, they exhibit an increased capacity for antigen uptake. ABCs were also compared with germinal center (GC) B cells, which are antigen activated B cell population. There are several phenotypic similarities between ABCs and GC B cells, but GC B cells do not produce proinflammatory cytokines or take up antigen. While T cell proliferation and activation is induced by both FO B and ABCs in an antigen-dependent manner, ABCs induce stronger T cell receptor signaling in naïve CD4+ T cells and preferentially induce differentiation of T follicular helper (Tfh) cells. We found that ABCs exhibit a distinct transcriptomic profile which is focused on metabolism, cytokine signaling and antigen uptake and processing. ABCs exhibit an increase in both glycolysis and oxidative phosphorylation compared to FO B cells. Treatment of ABCs with metformin suppresses antigen presentation by decreasing antigen uptake, resulting in decreased Tfh differentiation. Taken together, these findings define a fundamental connection between metabolism and function within ABCs.


Asunto(s)
Linfocitos B , Metformina , Animales , Ratones , Presentación de Antígeno , Autoinmunidad , Citocinas , Metformina/farmacología , Ratones Congénicos
18.
Exp Ther Med ; 26(4): 490, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37745042

RESUMEN

A desmoid tumor is a fibroblastic proliferation of mesenchymal origin, which has no metastasizing potential but is locally aggressive. Although treatment has shifted to observation and active surveillance for newly diagnosed patients with desmoid tumors, intra-abdominal mesenteric tumors or tumors that persistently grow and provoke symptoms may need prompt surgical treatment. There have only been a small number of case reports that illustrate large sporadic intra-abdominal mesentery-deriving desmoid tumors in which the longest diameter was ≥19 cm. In the present study, an adolescent male patient with a rapidly growing 38-cm long sporadic intra-abdominal desmoid tumor of mesenchymal origin is reported. The patient was treated with chemotherapy followed by surgical resection due to non-responsiveness and progression of symptoms, then with maintenance adjuvant chemotherapy to prevent recurrence due to the large size of the tumor. Despite the rapid growth of the tumor and its high occupancy in the intra-abdominal cavity, an R0 resection was successful with organ preservation. The patient has been recurrence-free for 2 years, and further follow-up is expected in the future.

19.
J Surg Oncol ; 128(8): 1365-1371, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37732720

RESUMEN

BACKGROUND: This study aimed to review the magnetic resonance imaging (MRI) features of patients with low rectal cancer (LRC) undergoing preoperative chemoradiotherapy (CRT) and investigate the risk factors for treatment failure after sphincter preserving surgery following preoperative CRT based on multidisciplinary approach. OBJECTIVES: Patients who underwent standard CRT and sphincter preserving radical surgery for LRC between January 2000 and December 2011 were retrospectively reviewed. Sphincter preservation failure (SPF) was defined as any one of the following: positive pathologic circumferential resection margin, local recurrence, failure to repair ileostomy, or permanent stoma formation due to anastomotic complications. RESULTS: Among the 191 patients, there were no overall significant differences between sphincter preservation success (n = 161) and SPF (n = 30) groups. SPF group showed a higher MRI circumferential resection margins (mrCRM) positive rate before and after CRT (before CRT: 33.3% vs. 16.1%, p = 0.027; after CRT: 23.3% vs. 6.2%, p = 0.002). Multivariate analysis showed that only mrCRM after CRT was associated with SPF (hazard ratio = 4.596, p = 0.005). SPF group showed worse 5-year cancer-specific survival (51% vs. 92.7%, p < 0.001). CONCLUSIONS: MRI-based assessment of the tumor after CRT plays a crucial role in predicting the success and feasibility of sphincter preservation as well as oncological outcomes in patients with LRC.


Asunto(s)
Márgenes de Escisión , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Terapia Neoadyuvante/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/cirugía , Quimioradioterapia/métodos , Insuficiencia del Tratamiento , Imagen por Resonancia Magnética , Resultado del Tratamiento , Estadificación de Neoplasias
20.
Int J Health Policy Manag ; 12: 7390, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37579357

RESUMEN

BACKGROUND: Pneumonia is one of the leading causes of hospital admission in the United States with a global health burden of about 6.8 million hospitalizations and 1.1 million deaths in patients over 65 years old in 2015. This study aimed to identify possible patient and hospital-related risk factors for in-hospital pneumonia death across US hospitals. METHODS: The National Inpatient Sample (NIS) was used to identify nationwide pneumonia patients (n=374 766, weighted n=1 873 828) from 2016 to 2019. We examined the characteristics of the study sample and their association with in-hospital death. Multivariate survey logistic regression models were used to identify risk factors. RESULTS: During the study periods, in-hospital death rates continuously decreased (2.45% in 2016 to 2.19% in 2019). Descriptive statistics showed that patient and hospital factors had varied in-hospital death rates. Survey logistic regression results suggested that male, very low income, non-Medicare, government hospitals, rural hospitals, and specific hospital regions were associated with higher in-hospital death rates than their reference groups. CONCLUSION: Socioeconomic factors, including income and insurance, are associated with pneumonia mortality. Census region, hospital ownership, and rural location are also related to in-hospital mortality. Such findings in underserved, impoverished, and rural areas to identify possible health disparities.


Asunto(s)
Hospitalización , Neumonía , Humanos , Masculino , Estados Unidos/epidemiología , Anciano , Mortalidad Hospitalaria , Hospitales , Pacientes Internos
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