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1.
Geriatr Orthop Surg Rehabil ; 15: 21514593241280926, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39372372

RESUMEN

Introduction: We aimed to describe patient awareness regarding fall prevention and education, perceived causes of falls, and changes in attitude after experiencing a fall through interviews with older Korean patients who experienced falls with resultant hip fractures. Materials and Methods: We conducted face-to-face semi-structured in-depth interviews with 11 patients who were admitted to Kangbuk Samsung Hospital for hip fractures caused by falls and were referred to the Department of Rehabilitation Medicine for postsurgical rehabilitation between June 2022 and June 2023. The data were analyzed using the phenomenological method developed by Colaizzi. Results: Before hip fracture, none of the patients had received fall prevention education or perceived its necessity; however, they recognized its necessity retrospectively. Participants described the causes of falls as carelessness, actions taken at the time of the fall, environmental factors, and decreased physical function. Most participants believed that falls could be prevented through personal caution and activity restrictions. Some mentioned fall prevention education, exercise, wearing appropriate shoes, environmental adjustments, and seeking assistance from others as methods of preventing future falls. Most patients reported adopting a safety-seeking attitude after experiencing hip fracture. Many patients had negative thoughts such as guilt or thoughts of death, whereas only a few reported increased interest in education and exercise. Conclusions: We observed a lack of fall prevention education, misunderstanding regarding the cause of falls, and negative psychological changes after experiencing hip fractures due to falls in older Korean individuals. Recognizing and managing patient perceptions is crucial for effective fall prevention, requiring both healthcare provider awareness and active participation from patients and caregivers.

2.
Radiat Oncol J ; 42(3): 171-180, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39354820

RESUMEN

Hypofractionated radiotherapy (RT) has become a trend in the modern era, as advances in RT techniques, including intensity-modulated RT and image-guided RT, enable the precise and safe delivery of high-dose radiation. Hypofractionated RT offers convenience and can reduce the financial burden on patients by decreasing the number of fractions. Furthermore, hypofractionated RT is potentially more beneficial for tumors with a low α/ß ratio compared with conventional fractionation RT. Therefore, hypofractionated RT has been investigated for various primary cancers and has gained status as a standard treatment recommended in the guidelines. In genitourinary (GU) cancer, especially prostate cancer, the efficacy, and safety of various hypofractionated dose schemes have been evaluated in numerous prospective clinical studies, establishing the standard hypofractionated RT regimen. Hypofractionated RT has also been explored for gynecological (GY) cancer, yielding relevant evidence in recent years. In this review, we aimed to summarize the representative evidence and current trends in clinical studies on hypofractionated RT for GU and GY cancers addressing several key questions. In addition, the objective is to offer suggestions for the available dose regimens for hypofractionated RT by reviewing protocols from previous clinical studies.

3.
Sci Adv ; 10(37): eado7089, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39259797

RESUMEN

Engineered heart tissues (EHTs) generated from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent powerful platforms for human cardiac research, especially in drug testing and disease modeling. Here, we report a flexible, three-dimensional electronic framework that enables real-time, spatiotemporal analysis of electrophysiologic and mechanical signals in EHTs under physiological loading conditions for dynamic, noninvasive, longer-term assessments. These electromechanically monitored EHTs support multisite measurements throughout the tissue under baseline conditions and in response to stimuli. Demonstrations include uses in tracking physiological responses to pharmacologically active agents and in capturing electrophysiological characteristics of reentrant arrhythmias. This platform facilitates precise analysis of signal location and conduction velocity in human cardiomyocyte tissues, as the basis for a broad range of advanced cardiovascular studies.


Asunto(s)
Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Ingeniería de Tejidos , Humanos , Ingeniería de Tejidos/métodos , Miocitos Cardíacos/fisiología , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes Inducidas/citología , Corazón/fisiología , Fenómenos Electrofisiológicos
4.
IEEE J Transl Eng Health Med ; 12: 542-549, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39155924

RESUMEN

OBJECTIVE: This study introduces a novel system that can simulate diverse mechanical properties of the human chest to enhance the experience of CPR training by reflecting realistic chest conditions of patients. METHODS: The proposed system consists of Variable stiffness mechanisms (VSMs) and Variable damper (VD) utilizing stretching silicone bands and dashpot dampers with controllable valves to modulate stiffness and damping, respectively. Cyclic loading was applied with a robot manipulator to the system. Compression force and displacement were measured and analyzed to evaluate the system's mechanical response. Long-term stability of the system was also validated. RESULTS: A non-linear response of the human chest under compression is realized through this design. Test results indicated non-linear force-displacement curves with hysteresis, similar to those observed in the chest of patients. Controlling the VSM and VD allowed for intentional changes in the slope and area of curves that are related to stiffness and damping, respectively. Stiffness and damping of the system were computed using performance test results. The stiffness ranged from 5.34 N/mm to 13.59 N/mm and the damping ranges from 0.127 N[Formula: see text] s/mm to 0.511 N[Formula: see text] s/mm. These properties cover a significant portion of the reported mechanical properties of the human chests. The system demonstrated satisfactory stability even when it was subjected to maximum stiffness conditions of the long-term compression test. CONCLUSION: The system is capable of emulating the mechanical properties and behavior of the human chests, thereby enhancing the CPR training experience.


Asunto(s)
Reanimación Cardiopulmonar , Maniquíes , Tórax , Humanos , Reanimación Cardiopulmonar/educación , Tórax/fisiología , Diseño de Equipo , Fenómenos Biomecánicos/fisiología
5.
J Leukoc Biol ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107254

RESUMEN

During recovery from septic shock, circulating mitochondrial N-formyl peptides (mtFPs) predispose to secondary infection by occupying formyl peptide receptor 1 (FPR1) on the neutrophil (polymorphonuclear leukocyte, PMN) membrane, suppressing cytosolic calcium ([Ca2+]i)-dependent responses to secondarily encountered bacteria. However, no study has yet investigated therapeutic clearance of circulating mtFPs in clinical settings. Thus, we studied how to remove mtFPs from septic-shock plasma and whether such removal could preserve cell-surface FPR1 and restore sepsis-induced PMN dysfunction by normalizing [Ca2+]i flux. In in vitro model systems, mtFP removal rescued PMN FPR1-mediated [Ca2+]i flux and chemotaxis that had been suppressed by prior mtFP exposure. However, PMN functional recovery occurred in a stepwise fashion over 30 - 90 minutes. Intracellular Ca2+-calmodulin appears to contribute to this delay. In ex vivo model systems using blood samples obtained from patients with septic shock, anti-mtFP antibodies alone failed to eliminate mtFPs from septic-shock plasma or inhibit mtFP activity. We therefore created a beads-based anti-mtFP antibody cocktail (bb-AMfpA) by combining protein A/sepharose with antibodies specific for the most potent human mtFP chemoattractants. The bb-AMfpA treatment successfully removed those active mtFPs from septic-shock plasma. Furthermore, the bb-AMfpA treatment significantly restored chemotactic and bactericidal dysfunction of PMNs obtained from patients with septic shock who developed secondary infections. By clearing circulating mtFPs, the immobilized anti-mtFP antibody therapy prevented mtFP interactions with surface FPR1, thereby restoring [Ca2+]i-dependent PMN antimicrobial function in clinical septic-shock environments. This approach may help prevent the development of secondary, nosocomial infections in patients recovering from septic shock.

6.
Resuscitation ; 202: 110354, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39122176

RESUMEN

AIM OF THE STUDY: We evaluated whether an artificial intelligence (AI)-driven robot cardiopulmonary resuscitation (CPR) could improve hemodynamic parameters and clinical outcomes. METHODS: We developed an AI-driven CPR robot which utilizes an integrated feedback system with an AI model predicting carotid blood flow (CBF). Twelve pigs were assigned to the AI robot group (n = 6) and the LUCAS 3 group (n = 6). They underwent 6 min of CPR after 7 min of ventricular fibrillation. In the AI robot group, the robot explored for the optimal compression position, depth and rate during the first 270-second period, and continued CPR with the optimal setup during the next 90-second period and beyond. The primary outcome was CBF during the last 90-second period. The secondary outcomes were coronary perfusion pressure (CPP), end-tidal carbon dioxide level (ETCO2) and return of spontaneous circulation (ROSC). RESULTS: The AI model's prediction performance was excellent (Pearson correlation coefficient = 0.98). CBF did not differ between the two groups [estimate and standard error (SE), -23.210 ± 20.193, P = 0.250]. CPP, ETCO2 level and rate of ROSC also did not show difference [estimate and SE, -0.214 ± 7.245, P = 0.976 for CPP; estimate and SE, 1.745 ± 3.199, P = 0.585 for ETCO2; 5/6 (83.3%) vs. 4/6 (66.7%), P = 1.000 for ROSC). CONCLUSION: This study provides proof of concept that an AI-driven CPR robot in porcine cardiac arrest is feasible. Compared to a LUCAS 3, an AI-driven CPR robot produced comparable hemodynamic and clinical outcomes.


Asunto(s)
Inteligencia Artificial , Reanimación Cardiopulmonar , Paro Cardíaco , Robótica , Animales , Reanimación Cardiopulmonar/métodos , Reanimación Cardiopulmonar/instrumentación , Porcinos , Robótica/instrumentación , Robótica/métodos , Paro Cardíaco/terapia , Paro Cardíaco/fisiopatología , Modelos Animales de Enfermedad , Hemodinámica/fisiología , Fibrilación Ventricular/terapia , Fibrilación Ventricular/fisiopatología , Arterias Carótidas/fisiopatología
7.
Am J Emerg Med ; 83: 69-75, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38976929

RESUMEN

OBJECTIVES: To determine whether there is a difference in antibiotic administration time and prognosis in afebrile sepsis patients compared to febrile sepsis patients. METHODS: This was retrospective multicenter observational study. Data collected from three referral hospitals. Data were collected from May 2014 through February 2016 under the SEPSIS-2 criteria and from March 2016 to April 2020 under the newly released SEPSIS-3 criteria. Patients were divided into two groups based on body temperature: afebrile (<37.3 °C) and febrile (≥37.3 °C). The relationship between initial body temperature and 28-day mortality were analyzed using multivariable logistic regression. The subgroup analysis was conducted on patients with complete Hour-1 bundle performance records. RESULTS: We included 4293 patients in this study. Initial body temperatures in 28-day survivors were significantly higher than in 28-day non-survivors (37.5 °C ± 1.2 °C versus 37.1 °C ± 1.2 °C, p < 0.01). Multivariable logistic regression analysis was performed in afebrile and febrile sepsis patients. Adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.76 (95% Confidence interval 1.46-2.12). As a result of performing the Hour-1 bundle, the number of patients who received antibiotics within 1 h was smaller in the afebrile sepsis patients (323/2076, 15.6%) than in the febrile sepsis patients (395/2156, 18.3%) (p = 0.02). In the subgroup analysis of patients with complete Hour-1 bundle performance records adjusted odds ratio of afebrile sepsis patients for 28-day mortality was 1.68 (95% Confidence interval 1.34-2.11). The febrile sepsis patients received antibiotics faster than the afebrile sepsis patients (175.5 ± 207.9 versus 209.3 ± 277.9, p < 0.01). CONCLUSIONS: Afebrile sepsis patients were associated with higher 28-day mortality compared to their febrile counterparts and were delayed in receiving antibiotics. This underscores the need for improved early detection and treatment strategies for the afebrile sepsis patients.


Asunto(s)
Antibacterianos , Visitas a la Sala de Emergencias , Servicio de Urgencia en Hospital , Fiebre , Sepsis , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Temperatura Corporal , Visitas a la Sala de Emergencias/estadística & datos numéricos , Fiebre/tratamiento farmacológico , Mortalidad Hospitalaria , Modelos Logísticos , Pronóstico , Estudios Retrospectivos , Sepsis/tratamiento farmacológico , Sepsis/mortalidad , Tiempo de Tratamiento/estadística & datos numéricos
8.
Radiat Oncol J ; 42(2): 104-115, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38946072

RESUMEN

Several recent studies have investigated the use of hypofractionated radiotherapy (HFRT) for various cancers. However, HFRT for non-small cell lung cancer (NSCLC) with or without concurrent chemotherapy is not yet widely used because of concerns about serious side effects and the lack of evidence for improved treatment results. Investigations of HFRT with concurrent chemotherapy in NSCLC have usually been performed in single-arm studies and with a small number of patients, so there are not yet sufficient data. Therefore, the Korean Society for Radiation Oncology Practice Guidelines Committee planned this review article to summarize the evidence on HFRT so far and provide it to radiation oncology clinicians. In summary, HFRT has demonstrated promising results, and the reviewed data support its feasibility and comparable efficacy for the treatment of locally advanced NSCLC. The incidence and severity of esophageal toxicity have been identified as major concerns, particularly when treating large fraction sizes. Strategies, such as esophagus-sparing techniques, image guidance, and dose constraints, may help mitigate this problem and improve treatment tolerability. Continued research and clinical trials are essential to refine treatment strategies, identify optimal patient selection criteria, and enhance therapeutic outcomes.

9.
Cancer Res Treat ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38965925

RESUMEN

Purpose: This study aimed to assess prognostic factors associated with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and to predict 5-year survival based on these factors. Materials and Methods: Patients who underwent definitive hepatectomy from 2006 to 2022 at a single institution was retrospectively analyzed. Inclusion criteria involved a pathologically confirmed diagnosis of cHCC-CCA. Results: A total of 80 patients with diagnosed cHCC-CCA were included in the analysis. The median progression-free survival (PFS) was 15.6 months, while distant metastasis-free survival (DMFS), hepatic progression-free survival (HPFS), and overall survival (OS) were 50.8, 21.5, and 85.1 months, respectively. In 52 cases of recurrence, intrahepatic recurrence was the most common initial recurrence (34/52), with distant metastasis in 17 cases. Factors associated with poor DMFS included tumor necrosis, lymphovascular invasion (LVI), perineural invasion and histologic compact type. Postoperative CA19-9, tumor necrosis, LVI, and close/positive margin were associated with poor overall survival. LVI emerged as a key factor affecting both DMFS and OS, with a 5-year OS of 93.3% for patients without LVI compared to 35.8% with LVI. Based on these factors, a nomogram predicting 3-year and 5-year DMFS and OS was developed, demonstrating high concordance with actual survival in the cohort (Harrell C-index 0.809 for OS, 0.801 for DMFS, respectively). Conclusion: The prognosis of cHCC-CCA is notably poor when combined with lymphovascular invasion. Given the significant impact of adverse features, accurate outcome prediction is crucial. Moreover, consideration of adjuvant therapy may be warranted for patients exhibiting poor survival and increased risk of local recurrence or distant metastasis.

10.
BMB Rep ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38919019

RESUMEN

The utilization of multi-omics research has gained popularity in clinical investigations. However, effectively managing and merging extensive and diverse datasets presents a challenge due to its intricacy. This research introduces a Multi-Omics Analysis Sandbox Toolkit, an online platform designed to facilitate the exploration, integration, and visualization of datasets ranging from single-omics to multi-omics. This platform establishes connections between clinical data and omics information, allowing for versatile analysis and storage of both single and multi-omics data. Additionally, users can repeatedly utilize and exchange their findings within the platform. This toolkit offers diverse alternatives for data selection and gene set analysis. It also presents visualization outputs, potential candidates, and annotations. Furthermore, this platform empowers users to collaborate by sharing their datasets, analyses, and conclusions with others, thus enhancing its utility as a collaborative research tool. This Multi-Omics Analysis Sandbox Toolkit stands as a valuable asset in comprehensively grasping the influence of diverse factors in diseases and pinpointing potential biomarkers.

11.
Cancer Med ; 13(7): e7156, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38572934

RESUMEN

IMPORTANCE: The COVID-19 pandemic led to reductions in primary care and cancer screening visits, which may delay detection of some cancers. The impact on incidence has not been fully quantified. We examined change in cancer incidence to determine how the COVID-19 pandemic may have altered the characteristics of cancers diagnosed among women. METHODS: This study included female patients aged ≥18 years and diagnosed with breast (n = 9489), colon (n = 958), pancreatic (n = 669), or uterine (n = 1991) cancer at three hospitals in North Carolina. Using interrupted time series, we compared incidence of cancers diagnosed between March 2020 and November 2020 (during pandemic) with cancers diagnosed between January 2016 and February 2020 (pre-pandemic). RESULTS: During the pandemic, incidence of breast and uterine cancers was significantly lower than expected compared to pre-pandemic (breast-18%, p = 0.03; uterine -20%, p = 0.05). Proportions of advanced pathologic stage and hormone receptor-negative breast cancers, and advanced clinical stage and large size uterine cancers were more prevalent during the pandemic. No significant changes in incidence were detected for pancreatic (-20%, p = 0.08) or colon (+14%, p = 0.30) cancers. CONCLUSION AND RELEVANCE: In women, the COVID-19 pandemic resulted in a significant reduction in the incidence of breast and uterine cancers, but not colon or pancreatic cancers. A change in the proportion of poor prognosis breast and uterine cancers suggests that some cancers that otherwise would have been diagnosed at an earlier stage will be detected in later years. Continued analysis of long-term trends is needed to understand the full impact of the pandemic on cancer incidence and outcomes.


Asunto(s)
Neoplasias de la Mama , COVID-19 , Neoplasias Uterinas , Femenino , Humanos , Adolescente , Adulto , Pandemias , COVID-19/epidemiología , North Carolina/epidemiología , Neoplasias de la Mama/patología , Neoplasias Uterinas/epidemiología , Colon/patología , Incidencia
12.
Radiat Oncol J ; 42(1): 17-31, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38549381

RESUMEN

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low α/ß ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options.

13.
Sci Rep ; 14(1): 4279, 2024 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383562

RESUMEN

The purpose of study was to evaluate that kallistatin deficiency causes excessive production of reactive oxygen species and exacerbates neuronal injury after cardiac arrest. For in vitro study, kallistatin knockdown human neuronal cells were given ischemia-reperfusion injury, and the oxidative stress and apoptosis were evaluated. For clinical study, cardiac arrest survivors admitted to the ICU were divided into the good (CPC 1-2) and poor (CPC 3-5) 6-month neurological outcome groups. The serum level of kallistatin, Nox-1, H2O2 were measured. Nox-1 and H2O2 levels were increased in the kallistatin knockdown human neuronal cells with ischemia-reperfusion injury (p < 0.001) and caspase-3 was elevated and apoptosis was promoted (SERPINA4 siRNA: p < 0.01). Among a total of 62 cardiac arrest survivors (16 good, 46 poor), serum kallistatin were lower, and Nox-1 were higher in the poor neurological group at all time points after admission to the ICU (p = 0.013 at admission; p = 0.020 at 24 h; p = 0.011 at 72 h). At 72 h, H2O2 were higher in the poor neurological group (p = 0.038). Kallistatin deficiency exacerbates neuronal ischemia-reperfusion injury and low serum kallistatin levels were associated with poor neurological outcomes in cardiac arrest survivors.


Asunto(s)
Paro Cardíaco , Daño por Reperfusión , Serpinas , Humanos , Peróxido de Hidrógeno
15.
Cell Genom ; 4(2): 100499, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38359788

RESUMEN

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.


Asunto(s)
Reordenamiento Génico , Translocación Genética , Humanos , Animales , Ratones , Mutación , Genómica , Inversión Cromosómica , Mamíferos
16.
PLoS One ; 19(1): e0297057, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38241416

RESUMEN

BACKGROUND: Recently, we developed a chest compression device that can move the chest compression position without interruption during CPR and be remotely controlled to minimize rescuer exposure to infectious diseases. The purpose of this study was to compare its performance with conventional mechanical CPR device in a mannequin and a swine model of cardiac arrest. MATERIALS AND METHODS: A prototype of a remote-controlled automatic chest compression device (ROSCER) that can change the chest compression position without interruption during CPR was developed, and its performance was compared with LUCAS 3 in a mannequin and a swine model of cardiac arrest. In a swine model of cardiac arrest, 16 male pigs were randomly assigned into the two groups, ROSCER CPR (n = 8) and LUCAS 3 CPR (n = 8), respectively. During 5 minutes of CPR, hemodynamic parameters including aortic pressure, right atrial pressure, coronary perfusion pressure, common carotid blood flow, and end-tidal carbon dioxide partial pressure were measured. RESULTS: In the compression performance test using a mannequin, compression depth, compression time, decompression time, and plateau time were almost equal between ROSCER and LUCAS 3. In a swine model of cardiac arrest, coronary perfusion pressure showed no difference between the two groups (p = 0.409). Systolic aortic pressure and carotid blood flow were higher in the LUCAS 3 group than in the ROSCER group during 5 minutes of CPR (p < 0.001, p = 0.008, respectively). End-tidal CO2 level of the ROSCER group was initially lower than that of the LUCAS 3 group, but was higher over time (p = 0.022). A Kaplan-Meier survival analysis for ROSC also showed no difference between the two groups (p = 0.46). CONCLUSION: The prototype of a remote-controlled automated chest compression device can move the chest compression position without interruption during CPR. In a mannequin and a swine model of cardiac arrest, the device showed no inferior performance to a conventional mechanical CPR device.


Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco , Masculino , Animales , Porcinos , Proyectos Piloto , Maniquíes , Paro Cardíaco/terapia , Presión , Hemodinámica
17.
EMBO Mol Med ; 16(1): 40-63, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38177528

RESUMEN

Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Secreted human tryptophanyl-tRNA synthetase 1 (WARS1), an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4 against infection, activates the genes that signify the hyperinflammatory sepsis phenotype. High plasma WARS1 levels stratified the early death of critically ill patients with sepsis, along with elevated levels of cytokines, chemokines, and lactate, as well as increased numbers of absolute neutrophils and monocytes, and higher Sequential Organ Failure Assessment (SOFA) scores. These symptoms were recapitulated in severely ill septic mice with hypercytokinemia. Further, injection of WARS1 into mildly septic mice worsened morbidity and mortality. We created an anti-human WARS1-neutralizing antibody that suppresses proinflammatory cytokine expression in marmosets with endotoxemia. Administration of this antibody into severe septic mice attenuated cytokine storm, organ failure, and early mortality. With antibiotics, the antibody almost completely prevented fatalities. These data imply that blood-circulating WARS1-guided anti-WARS1 therapy may provide a novel theranostic strategy for life-threatening systemic hyperinflammatory sepsis.


Asunto(s)
Sepsis , Triptófano-ARNt Ligasa , Humanos , Animales , Ratones , Triptófano-ARNt Ligasa/genética , Medicina de Precisión , Citocinas/metabolismo , Quimiocinas
18.
Gynecol Oncol ; 182: 45-50, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38246046

RESUMEN

OBJECTIVE: Among cervical adenocarcinomas, well-differentiated gastric adenocarcinoma of the uterine cervix (WD-GAS), previously termed adenoma malignum (minimal deviation adenocarcinoma) is not well understood. Because of its rarity and difficulty in diagnosis, there is no standard care for WD-GAS. Thus, we conducted the first multicenter retrospective study on WD-GAS to clarify prognostic factors for long-term survival and recurrence. METHODS: Patients diagnosed with WD-GAS at eight hospitals participated in this multi-center study. Overall survival (OS) and recurrence-free survival (RFS) were calculated with the Kaplan-Meier method. Additionally, OS between the early and advanced FIGO stage groups were compared with the log-rank test. Cox regression analysis was conducted to identify significant factors associated with recurrence-free survival (RFS). RESULTS: A total of 73 patients from eight hospitals in South Korea were included in the analysis. The median follow-up period was 44.8 months, and all patients underwent curative surgical intervention as the primary treatment. Recurrence was observed in 17 patients (23.3%). Ten patients had locoregional recurrence, four patients had distant metastasis, and three patients presented with both locoregional recurrence and distant metastasis. The Cox regression analysis identified several statistically significant factors associated with RFS, including vaginal invasion (VI), parametrial invasion (PMI), resection margin (RM), and nodal and lymphovascular invasion (LVI). When considering these five factors together, patients without any of the factors exhibited recurrence-free survival (RFS) of 97.0% at three years and those with more than one of these factors had a 3-year RFS of 65.4% (P < 0.001). CONCLUSION: WD-GAS showed relatively high locoregional recurrence rate. Positive PMI, VI, RM, nodal involvement, and LVI were associated with a significant increase in recurrence or distant metastasis rates.


Asunto(s)
Adenocarcinoma , Adenoma , Neoplasias del Cuello Uterino , Femenino , Humanos , Estudios Retrospectivos , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/patología , Pronóstico , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Adenocarcinoma/cirugía , Adenoma/patología
19.
Shock ; 61(1): 55-60, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37878497

RESUMEN

ABSTRACT: Objective: This study aimed to test whether the prognostic value of tryptophanyl-tRNA synthetase 1 (WARS1) for 28-day mortality in patients with sepsis was affected by monocytopenia. Methods: A prospective analysis of retrospectively collected samples from 74 sepsis patients was performed. WARS1, C-reactive protein (CRP), and procalcitonin were measured at admission and 24 and 72 h after admission. The prognostic value of WARS1, CRP, and procalcitonin for 28-day mortality was compared using repeated measures analysis of variance and the area under the receiver operating characteristic curve (AUROC). All analyses were performed in patients with or without monocytopenia, defined as an absolute monocyte count less than 0.1 × 10 9 cells/L. Results: WARS1 levels differed significantly between survivors and nonsurvivors when all patients and patients without monocytopenia were assessed ( P = 0.008, P < 0.001, respectively). In contrast, the WARS1 level did not differ between survivors and nonsurvivors with monocytopenia. C-reactive protein and procalcitonin levels were not different between survivors and nonsurvivors regardless of whether they had monocytopenia. The AUROCs of WARS1 at admission and 24 h for mortality were significantly higher in patients without monocytopenia (0.830, 0.818) than in patients with monocytopenia (0.232, 0.196; P < 0.001, both). When patients without monocytopenia were analyzed, the AUROCs of WARS1 for mortality were 0.830 and 0.818 at admission and 24 h, respectively, which were significantly higher than those of CRP (0.586, 0.653) and procalcitonin (0.456, 0.453) at the same time points ( P = 0.024 and 0.034, respectively). Conclusion: WARS1 is a useful biomarker for prognosis in sepsis patients without monocytopenia.


Asunto(s)
Sepsis , Triptófano-ARNt Ligasa , Humanos , Pronóstico , Proteína C-Reactiva/metabolismo , Polipéptido alfa Relacionado con Calcitonina , Estudios Retrospectivos , Biomarcadores , Curva ROC
20.
Int J Biol Macromol ; 253(Pt 5): 127069, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37751819

RESUMEN

We propose a general green method coupled with a solid-state vibration ball milling strategy for the synthesis of various metal nanoparticles (MNPs), employing a polymeric carbohydrate dextran (Dx) as a reducing and stabilizing molecule. The synthesis of size-controlled Dx-based MNPs (Dx@MNPs), featuring comparatively narrow size distributions, was achieved by controlling the mass ratio of the reactants, reaction time, frequency of the vibration ball mill, and molecular weight of Dx. Notably, this process was conducted at ambient temperatures, without the aid of solvents and accelerating agents, such as NaOH, and conventional reductants as well as stabilizers. Thermal properties of the resulting Dx@MNPs nanocomposites were extensively investigated, highlighting the influence of metal precursors and reaction conditions. Furthermore, the catalytic activity of synthesized nanocomposites was evaluated through the reduction reaction of 4-nitrophenol, exhibiting great catalytic performance. In addition, we demonstrated the excellent biocompatibility of the as-prepared Dx@MNPs toward human embryonic kidney (HEK-293) cells, revealing their potential for anticancer activities. This novel green method for synthesizing biocompatible MNPs with Dx expands the horizons of carbohydrate-based materials as well as MNP nanocomposites for large-scale synthesis and controlled size distribution for various industrial and biomedical applications.


Asunto(s)
Dextranos , Nanopartículas del Metal , Humanos , Solventes , Células HEK293
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