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1.
World J Surg Oncol ; 22(1): 171, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926860

RESUMEN

INTRODUCTION: The safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the clinicopathological features and to evaluate the safety and survival prognosis of CRS + HIPEC combined with urinary tract resection and reconstruction. METHODS: The patients who underwent urinary tract resection and reconstruction as part of CRS surgery were retrospectively selected from our disease-specific database for analysis. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were studied using a descriptive approach and the K-M analysis with log-rank comparison. RESULTS: Forty-nine patients were enrolled. Perioperative serious AEs (SAEs) were observed in 11 patients (22.4%), with urinary SAEs occurring in 3 patients (6.1%). Additionally, there were 23 cases (46.8%) involving urinary adverse events (UAEs). The median overall survival (OS) in the entire cohort was 59.2 (95%CI: 42.1-76.4) months. The median OS of the UAE group and No-UAE group were 59.2 months (95%CI not reached), and 50.5 (95%CI: 11.5 to 89.6) months, respectively, with no significant difference (P = 0.475). Furthermore, there were no significant differences in OS based on the grade of UAEs or the number of UAEs (P = 0.562 and P = 0.622, respectively). CONCLUSION: The combination of CRS + HIPEC with urinary tract resection and reconstruction is associated with a high incidence of Grade I-II UAEs, which do not have an impact on OS. The safety profile of this combined technique is acceptable. However, this is a retrospective single-center single-arm analysis, with limitations of generalizability and potential selection bias. The findings need high-level validation.


Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Quimioterapia Intraperitoneal Hipertérmica , Humanos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Pronóstico , Anciano , Hipertermia Inducida/métodos , Hipertermia Inducida/efectos adversos , Hipertermia Inducida/mortalidad , Quimioterapia Intraperitoneal Hipertérmica/métodos , Estudios de Seguimiento , Adulto , Procedimientos Quirúrgicos de Citorreducción/métodos , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Terapia Combinada , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/patología , Sistema Urinario/cirugía , Sistema Urinario/patología , Procedimientos Quirúrgicos Urológicos/métodos , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/etiología
2.
Neurotherapeutics ; : e00382, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38852008

RESUMEN

BACKGROUND: The ARAIS trial didn't demonstrate argatroban significantly improve functional outcome at 90 days in acute ischemic stroke. We conducted post hoc analysis of ARAIS to investigate whether baseline neurological deficit was associated with outcomes. METHODS: Patients without endovascular therapy who met screening criteria as protocol and completed argatroban treatment were enrolled and classified into two subgroups according to NIHSS score at admission. Primary outcome was excellent functional outcome at 90 days, defined as mRS score of 0 to 1. Early neurological deterioration (END), defined as an increase of ≥4 in the NIHSS score from baseline within 48 hours, was investigated as secondary outcome. Compared with alteplase alone, we investigated treatment effect of argatroban plus alteplase on outcomes in subgroups and interaction with subgroups. RESULTS: A total of 675 patients from full analysis set were included: 390 were assigned into NIHSS score <10 subgroup and 285 into NIHSS score ≥10 subgroup. For primary outcome, there was similar treatment effect between argatroban plus alteplase and alteplase alone in NIHSS score ≥10 subgroup (adjusted RD, 5.8%; 95% CI, -6.0% to 17.5%; P = 0.33) and in NIHSS score <10 subgroup (adjusted RD, -1.4%; 95% CI, -9.9% to 7.1%; P = 0.75), and no significant interaction (P = 0.43). Occurrence of early neurological deterioration within 48 hours were significantly lower in NIHSS score ≥10 subgroup, compared with NIHSS score <10 subgroup (P = 0.006). CONCLUSION: Among patients with NIHSS score ≥10, argatroban plus alteplase could safely reduce END within 48 hours.

3.
BMC Musculoskelet Disord ; 25(1): 276, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600475

RESUMEN

BACKGROUND: Traditional total hip arthroplasty (THA) using the direct anterior approach (DAA) requires a hip extension. This study aimed to compare the clinical outcomes of patients undergoing THA with DAA using either the no hip extension (NHE) or the traditional hip extension (THE) strategy. METHODS: A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 123 patients treated between January 2020 and November 2021. The patients were categorised into two groups: NHE (84 patients) and THE (39 patients). RESULTS: The NHE group exhibited shorter operative time and had more male participants with higher ages. Comparable outcomes were observed in the visual analogue scale, Harris Hip, and Oxford Hip scores at the final follow-up. Furthermore, complications were observed in the NHE and THE groups, including two and one greater trochanteric fractures and three and one transfusions, respectively. CONCLUSIONS: Compared to the THE, employing the NHE strategy during THA with DAA in elderly and young female patients resulted in comparable clinical outcomes with several advantages, such as favourable surgical time. The NHE method also exhibited good safety and effectiveness. Therefore, the NHE strategy may be a favourable option for elderly and young female patients.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Humanos , Masculino , Femenino , Anciano , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Radiografía , Tempo Operativo
4.
Pharmacol Ther ; 256: 108596, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38301770

RESUMEN

Inherited cardiac arrhythmias are a group of genetic diseases predisposing to sudden cardiac arrest, mainly resulting from variants in genes encoding cardiac ion channels or proteins involved in their regulation. Currently available therapeutic options (pharmacotherapy, ablative therapy and device-based therapy) can not preclude the occurrence of arrhythmia events and/or provide complete protection. With growing understanding of the genetic background and molecular mechanisms of inherited cardiac arrhythmias, advancing insight of stem cell technology, and development of vectors and delivery strategies, gene therapy and stem cell therapy may be promising approaches for treatment of inherited cardiac arrhythmias. Recent years have witnessed impressive progress in the basic science aspects and there is a clear and urgent need to be translated into the clinical management of arrhythmic events. In this review, we present a succinct overview of gene and cell therapy strategies, and summarize the current status of gene and cell therapy. Finally, we discuss future directions for implementation of gene and cell therapy in the therapy of inherited cardiac arrhythmias.


Asunto(s)
Arritmias Cardíacas , Muerte Súbita Cardíaca , Humanos , Arritmias Cardíacas/terapia , Arritmias Cardíacas/tratamiento farmacológico , Canales Iónicos/genética , Tratamiento Basado en Trasplante de Células y Tejidos
5.
J Nat Med ; 78(2): 427-438, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38334900

RESUMEN

Angelica dahurica (A. dahurica) has a wide range of pharmacological effects, including analgesic, anti-inflammatory and hepatoprotective effects. In this study, we investigated the effect of A. dahurica extract (AD) and its effective component bergapten (BG) on hepatic fibrosis and potential mechanisms. Hepatic fibrosis was induced by intraperitoneal injection with carbon tetrachloride (CCl4) for 1 week, and mice were administrated with AD or BG by gavage for 1 week before CCl4 injection. Hepatic stellate cells (HSCs) were stimulated by transforming growth factor-ß (TGF-ß) and cultured with AD, BG, GW4064 (FXR agonist) or Guggulsterone (FXR inhibitor). In CCl4-induced mice, AD significantly decreased serum aminotransferase, reduced excess accumulation of extracellular matrix (ECM), inhibited caspase-1 and IL-1ß, and increased FXR expressions. In activated HSCs, AD suppressed the expressions of α-SMA, collagen I, and TIMP-1/MMP-13 ratio and inflammatory factors, functioning as FXR agonist. In CCl4-induced mice, BG significantly improved serum transaminase and histopathological changes, reduced ECM excessive deposition, inflammatory response, and activated FXR expression. BG increased FXR expression and inhibited α-SMA and IL-1ß expressions in activated HSCs, functioning as GW4064. FXR deficiency significantly attenuated the decreasing effect of BG on α-SMA and IL-1ß expressions in LX-2 cells. In conclusion, AD could regulate hepatic fibrosis by regulating ECM excessive deposition and inflammation. Activating FXR signaling by BG might be the potential mechanism of AD against hepatic fibrosis.


Asunto(s)
Cirrosis Hepática , Transducción de Señal , Ratones , Animales , 5-Metoxipsoraleno/efectos adversos , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Células Estrelladas Hepáticas , Factor de Crecimiento Transformador beta/farmacología , Hígado
6.
Chem Biodivers ; 21(6): e202301923, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38191840

RESUMEN

Two new C19-diterpenoid alkaloids of the lycoctonine-type (liangshanine A and liangshanine B) and nineteen known compounds (3-21) were isolated from the whole plant of Delphinium liangshanense W. T. Wang, and all the compounds were identified by different spectroscopic analyses, such as IR, HR-ESI-MS and NMR. All the compounds were isolated from this plant for the first time and tested for the anti-proliferation effects on MH7 A and SF9 cells to figure their anti-rheumatoid arthritis and anti-insect activity, but none of them showed remarkable activity.


Asunto(s)
Alcaloides , Delphinium , Diterpenos , Delphinium/química , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Animales , Proliferación Celular/efectos de los fármacos , Línea Celular , Spodoptera/efectos de los fármacos , Estructura Molecular , Humanos , Conformación Molecular
7.
Ann Surg Oncol ; 31(2): 1058-1068, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37865941

RESUMEN

PURPOSE: We aimed to evaluate the safety and efficacy of hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) and cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) patients who underwent diaphragm resection. METHODS: PC patients who underwent CRS with diaphragm resection were selected from a prospectively established database and were divided into hyperthermic intraperitoneal chemotherapy (HIPEC) and HITAC groups. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were compared between the two groups. RESULTS: Of 1168 CRS + HIPEC/HITACs, 102 patients were enrolled-61 HITAC patients and 41 HIPEC patients. In the HITAC and HIPEC groups, the incidence of grade III-V AEs was 29.5% versus 34.1% (p = 0.621). The pleural progression rates were 13.2 versus 18.9% (p = 0.462) and the median overall survival (OS) was 50.5 versus 52.7 months (p = 0.958). Median time to progression (TTP) in thoracic disease was not reached. There was no significant difference in perioperative AEs, TTP, and OS for total patients and the completeness of cytoreduction (CC) score subgroups (p > 0.05). Age ≥ 60 years (hazard ratio [HR] 4.162, p = 0.026) was an independent risk factor influencing pleural progression, and primary malignant peritoneal mesothelioma (MPM; HR 2.749, p = 0.016) and the presence of two or more serious AEs (SAEs; HR 7.294, p = 0.001) were independent risk factors influencing OS. CONCLUSIONS: HITAC can be performed in carefully selected PC patients who underwent diaphragm resection, with no worsening of the safety profile and a possible benefit for pleural progression. In those patients, age ≥ 60 years is associated with a shorter TTP of thoracic disease, while primary MPM and two or more perioperative SAEs are associated with worse OS.


Asunto(s)
Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Persona de Mediana Edad , Neoplasias Peritoneales/patología , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Diafragma/patología , Quimioterapia del Cáncer por Perfusión Regional , Tasa de Supervivencia
8.
Chinese Medical Ethics ; (6): 592-602, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1036473

RESUMEN

ObjectiveTo clarify the current situation and trend of the social application field of medical humanities in China, explore contributions and characteristics of interdisciplinary fields, and provide a reference for improving the disciplinary research system and forming disciplinary synergy. MethodsCiteSpace, a visual software, was used to cluster the keywords of the social application of medical humanities journals from 2010 to 2022, which were included in three major databases of CNKI, Wanfang Data, and VIP. The clusters were classified according to the functions of contemporary universities. This paper summarized the current social application fields of medical humanities in China and conducted a holistic analysis. ResultsThe current social application field of medical humanities in China included eight fields: education and teaching of medical humanities, construction of discipline professional, academic research on discipline ideology, application of medical scientific research work, medical health service and safety management, resolution of doctor-patient relationship and dispute, traditional Chinese medicine culture and humanistic spirit, and adaptation to the national strategic development concept respectively. ConclusionThere was an uneven tendency in the development of the social application field of medical humanities in China. The overall distribution of its social application fields showed a trend of “strong humanities education, strong academic research, strong medical safety, and weak cultural concepts”. Medical humanities education was the common focus of the social application of medical humanities in China.

9.
Chinese Medical Ethics ; (6): 248-252, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1026161

RESUMEN

On August 2-4,2023,the"Third Summit Forum on'Building a Community of Shared Future for Doctors and Patients'"was jointly organized by institutions such as the Chinese Medical Ethics,the Hospital Humanities Management and Talent Training Special Committee of the China Population and Culture Promotion Association,Center for Ethical Studies of Renmin University of China,the Newspaper for China's Physicians,the China Health Law Society,the China Anti-Cancer Association,and the China Association For Ethical Studies in Harbin.The conference arranged a sub-forum for the"Seminar on the Construction of Chinese Medical Humanities",with domestic medical humanities scholars attending the conference.After heated discussions at the seminar,the Scholars'Consensus on the Construction and Development of Chinese Medical Humanities was formed.It was proposed that in the new era,it is urgent to build the medical humanities discipline,as well as lead the academic integration and development of medical humanities under the core socialist values.At the same time,for the construction of the medical humanities discipline,it is necessary to optimize the organizational mechanism,prosper and develop the overall framework of the medical humanities discipline,accelerate the construction of a professional teaching team for the medical humanities discipline,promote the establishment of a new carrier medical humanities education and teaching in cultivating morality and nurturing talents,as well as focus on solving problems related to the cultivation of medical humanities graduate students.

10.
Surgery ; 174(4): 1041-1049, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37481423

RESUMEN

BACKGROUND: Intertrochanteric fracture in the geriatric population is associated with poor prognosis, which may be attributed to consistent stress and the systemic inflammatory response. Dexamethasone is an exogenous glucocorticoid commonly used in clinical practice for broad anti-inflammatory action. The purpose is to investigate whether a single preoperative low-dose dexamethasone can improve the in-hospital prognosis in geriatric intertrochanteric fracture patients undergoing internal fixation surgery. METHODS: Between June 2020 and October 2022, 219 eligible patients with intertrochanteric fractures were in this study. After meeting the inclusion and exclusion criteria, 160 patients were randomly allocated to the dexamethasone or placebo groups (80 patients who are geriatric with an intertrochanteric fracture in each group). The patients in the dexamethasone group received 10 mg (2 mL) of dexamethasone intravenously, whereas the patients in the placebo group received 2 mL of saline intravenously within 30 minutes before being sent to the operating room. The efficacy-related outcomes (the first bed-chair transfer ability, in-hospital mortality, and length of stay) and safety-related outcomes (infection events and hyperglycemia) were collected for analysis. RESULTS: There were no significant differences in the baseline characteristics between the 2 groups. The dexamethasone group had a significantly higher rate of the first bed-chair transfer than the placebo group (65.0% [52/80] vs 48.8% [39/80], relative risk = 1.46, 95% confidence interval = 1.02 to 2.11; P = .038). One patient in the dexamethasone group and 7 patients in the placebo group died during hospitalization (1.3% [1/80] vs 8.8% [7/80], relative risk = 0.92, 95% confidence interval = 0.86 to 0.99; P = .07). No differences were found in the length of stay, infections, and hyperglycemia between the 2 groups. CONCLUSION: A single preoperative low-dose of dexamethasone can improve the in-hospital prognosis (increase the ability of the first bed-chair transfer and potentially decrease the in-hospital mortality) in geriatric intertrochanteric fracture patients after internal fixation surgery.


Asunto(s)
Fracturas de Cadera , Hiperglucemia , Humanos , Anciano , Pronóstico , Hospitales , Fracturas de Cadera/cirugía , Hiperglucemia/etiología , Hiperglucemia/prevención & control , Dexametasona
11.
JAMA ; 329(24): 2135-2144, 2023 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-37367978

RESUMEN

Importance: Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. Objective: To investigate whether dual antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. Interventions: Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to -4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. Results: Among 760 eligible randomized patients (median [IQR] age, 64 [57-71] years; 223 [31.0%] women; median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% [95% CI, -1.5% to 6.2%]; crude relative risk, 1.38 [95% CI, 0.81-2.32]). The unadjusted lower limit of the 1-sided 97.5% CI was -1.5%, which is larger than the -4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. Conclusions and Relevance: Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03661411.


Asunto(s)
Fibrinolíticos , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Activador de Tejido Plasminógeno , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Cerebral/inducido químicamente , Fibrinolíticos/administración & dosificación , Fibrinolíticos/efectos adversos , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/efectos adversos , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del Tratamiento , Quimioterapia Combinada , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Administración Intravenosa , Clopidogrel/administración & dosificación , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Aspirina/administración & dosificación , Aspirina/efectos adversos , Aspirina/uso terapéutico , Estudios de Seguimiento , Anciano , Recuperación de la Función
12.
J Orthop Surg Res ; 18(1): 441, 2023 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-37337260

RESUMEN

OBJECTIVE: Postoperative delirium (POD) is a common complication along with poor prognosis in geriatric intertrochanteric fracture (ITF) patients. However, the prevention and treatment of POD remain unclear. Previous studies have confirmed that POD is essentially a consequence of neuro-inflammatory responses. Dexamethasone is a glucocorticoid with comprehensive anti-inflammatory effects, while a high dose of dexamethasone correlates with many side effects or even adverse consequences. Thus, this prospective study aims to discuss whether a single preoperative low-dose dexamethasone can reduce the impact of POD on geriatric ITF patients with internal fixation surgery. METHODS: Between June 2020 and October 2022, there were 219 consecutive ITF patients assessed in our department. Of the 219 ITF patients, 160 cases who met the inclusion and exclusion criteria were finally enrolled and randomly allocated to the dexamethasone group and the placebo group (80 geriatric ITF patients in each group) in this prospective study. The patients in the dexamethasone group received intravenous 10 mg (2 ml) dexamethasone while the patients in the placebo group received intravenous 2 ml saline in 30 min before being sent to the operating room, respectively. The baseline characteristics, surgical information, incidence and severity of POD as the efficacy-related outcomes, and infection events and hyperglycemia as safety-related outcomes (adverse events), were collected and analyzed between the two groups. The severity of POD was evaluated by Memorial Delirium Assessment Scale (MDAS) score. RESULTS: There were no differences in baseline characteristics and surgical information between the dexamethasone group and the placebo group. The dexamethasone group had a lower incidence of POD than the placebo group within the first 5 days after surgery [(9/80, 11.3% vs. 21/80, 26.3%, RR = 0.83, 95% CI 0.71-0.97, P = 0.015]. The dexamethasone group had lower MDAS scores (Mean ± SD) than the placebo group [13.2 ± 1.0 (range 11 to 15) vs. 15.48 ± 2.9 (range 9 to 20), P = 0.011, effect size = 0.514]. There were no differences in infection events and hyperglycemia between the two groups. CONCLUSIONS: A single preoperative low-dose dexamethasone may reduce the incidence and severity of POD in geriatric ITF patients with internal fixation surgery. TRIAL REGISTRATION: ChiCTR2200055281.


Asunto(s)
Delirio , Delirio del Despertar , Fracturas de Cadera , Humanos , Anciano , Delirio del Despertar/tratamiento farmacológico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos , Incidencia , Delirio/epidemiología , Delirio/etiología , Delirio/prevención & control , Fracturas de Cadera/cirugía , Fracturas de Cadera/tratamiento farmacológico , Dexametasona
13.
Philos Trans R Soc Lond B Biol Sci ; 378(1879): 20220174, 2023 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-37122214

RESUMEN

Atrial fibrillation (AF) is a very common cardiac arrhythmia with an estimated prevalence of 33.5 million patients globally. It is associated with an increased risk of death, stroke and peripheral embolism. Although genetic studies have identified a growing number of genes associated with AF, the definitive impact of these genetic findings is yet to be established. Several mechanisms, including electrical, structural and neural remodelling of atrial tissue, have been proposed to contribute to the development of AF. Despite over a century of exploration, the molecular and cellular mechanisms underlying AF have not been fully established. Current antiarrhythmic drugs are associated with a significant rate of adverse events and management of AF using ablation is not optimal, especially in cases of persistent AF. This review discusses recent advances in our understanding and management of AF, including new concepts of epidemiology, genetics and pathophysiological mechanisms. We review the current status of antiarrhythmic drug therapy for AF, new potential agents, as well as mechanism-based AF ablation. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.


Asunto(s)
Fibrilación Atrial , Humanos , Fibrilación Atrial/etiología , Fibrilación Atrial/genética , Investigación Biomédica Traslacional , Antiarrítmicos/uso terapéutico , Frecuencia Cardíaca
14.
Microbiol Spectr ; 11(3): e0308922, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37140456

RESUMEN

Drug resistance against bacteria and fungi has become common in recent years, and it is urgent to discover novel antimicrobial peptides to manage this problem. Many antimicrobial peptides from insects have been reported to have antifungal activity and are candidate molecules in the treatment of human diseases. In the present study, we characterized an antifungal peptide named blapstin that was isolated from the Chinese medicinal beetle Blaps rhynchopetera used in folk medicine. The complete coding sequence was cloned from the cDNA library prepared from the midgut of B. rhynchopetera. It is a 41-amino-acid diapause-specific peptide (DSP)-like peptide stabilized by three disulfide bridges and shows antifungal activity against Candida albicans and Trichophyton rubrum with MICs of 7 µM and 5.3 µM, respectively. The C. albicans and T. rubrum treated with blapstin showed irregular and shrunken cell membranes. In addition, blapstin inhibited the activity of C. albicans biofilm and showed little hemolytic or toxic activity on human cells and it is highly expressed in the fat body, followed by the hemolymph, midgut, muscle, and defensive glands. These results indicate that blapstin may help insects fight against fungi and showed a potential application in the development of antifungal reagents. IMPORTANCE Candida albicans is one of the conditional pathogenic fungi causing severe nosocomial infections. Trichophyton rubrum and other skin fungi are the main pathogens of superficial cutaneous fungal diseases, especially in children and the elderly. At present, antibiotics such as amphotericin B, ketoconazole, and fluconazole are the main drugs for the clinical treatment of C. albicans and T. rubrum infections. However, these drugs have certain acute toxicity. Long-term use can increase kidney damage and other side effects. Therefore, obtaining broad-spectrum antifungal drugs with high efficiency and low toxicity for the treatment of C. albicans and T. rubrum infections is a top priority. Blapstin is an antifungal peptide which shows activity against C. albicans and T. rubrum. The discovery of blapstin provides a novel clue for our understanding of the innate immunity of Blaps rhynchopetera and provides a template for designing antifungal drugs.


Asunto(s)
Escarabajos , Dermatomicosis , Animales , Niño , Humanos , Anciano , Antifúngicos/uso terapéutico , Candida albicans , Pruebas de Sensibilidad Microbiana , Dermatomicosis/tratamiento farmacológico , Péptidos/farmacología , Péptidos Antimicrobianos
15.
Ann Med ; 55(1): 1047-1057, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-36908232

RESUMEN

BACKGROUND: The value of plasma Platelet-Derived Growth Factor (PDGF) as a biomarker in predicting major adverse cardiovascular events (MACEs) in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. METHODS: A total of 242 patients with NSTEMI were enrolled in this observational cohort study. The correlation between PDGF and MACEs was evaluated during a five-year follow-up. Kaplan-Meier survival analysis with Cox proportional-hazards regression was used to identify predictive values of PDGF. RESULTS: The mean follow-up of NSTEMI patients was 1334 days. It was found that as the PDGF level increased, a significant uptrend in the incidence of MACEs and all-cause death, including the MACEs of 30 days, 180 days, 1 year, 5 years and the death of 1 year and 5 years (All Log-rank p < .05). Subgroup analysis further showed that PDGF had better predictive value for patients with age >65 years, GRACE score ≥140 and platelet count (PLT) >200 × 109/L. CONCLUSION: PDGF levels can predict short-term and long-term MACEs in NSTEMI patients after discharge, especially for patients with older age, higher GRACE score and baseline PLT > 200 × 109/L.Key messagesPDGF is a risk factor for short- and long-term MACEs in patients with STEMI.PDGF has a better prognostic value in patients with older age and PLT > 200 × 109/L.Baseline plasma PDGF levels were positively correlated with GRACE score.


Asunto(s)
Infarto del Miocardio sin Elevación del ST , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Anciano , Pronóstico , Biomarcadores , Factores de Riesgo
16.
BMC Musculoskelet Disord ; 24(1): 189, 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36915071

RESUMEN

OBJECTIVE: To design a standardized Tip-Apex Distance (STAD) and analyze the clinical significance of STAD in predicting cut-out in geriatric intertrochanteric fractures with internal fixation. METHODS: Firstly, we designed STAD according to the rule of TAD. We measured the STAD individually based on its own femoral head diameter (iFHD) instead of the known diameter of the lag screw in calculating TAD, resulting in that the STAD is simply the relative quantitation relationship of iFHD (the times of iFHD). In this study, we assumed that all the iFHD was 6D (1iFHD = 6D, or 1D = 1/6 of iFHD) in order for complete match of the Cleveland zone system, easy comparison of the STAD, and convenient identification for artificial intelligence. Secondly, we calculated and recorded all the STAD of cephalic fixator in 123 eligible ITF patients. Thirdly, we grouped all the ITF patients into the Failure and Non-failure groups according to whether cut-out or not, and analyzed the correlation between the cut-out and the STAD. RESULTS: Cleveland zone, Parker's ratio (AP), TAD, and STAD were associated with the cut-out in univariate analysis. However, only STAD was the independent predictor of the cut-out by multivariate analysis. No cut-out was observed when STAD ≤ 2D (1/3 of iFHD). The Receiver Operating Characteristic (ROC) curve indicated that STAD was a reliable predictor of cut-out, and the best cut-off value of STAD was 2.92D. Cut-out rate increased dramatically when STAD increased, especially when STAD > 3D (1/2 of iFHD). CONCLUSION: Essentially, the STAD is a relative quantitation relationship of iFHD. The STAD is a reliable measurement of cephalic fixator position in predicting cut-out in geriatric ITF patients with single-screw cephalomedullary nail fixations. For avoiding cut-out, the STAD should be no more than a half of iFHD. LEVEL OF EVIDENCE: Level III, Prognostic Study.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas de Cadera , Humanos , Anciano , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/cirugía , Fijación Intramedular de Fracturas/métodos , Inteligencia Artificial , Clavos Ortopédicos , Estudios Retrospectivos , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Resultado del Tratamiento
17.
Oncogene ; 42(15): 1247-1262, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36869127

RESUMEN

The limited success of immunotherapies targeting immune checkpoint inhibitors is largely ascribed to the lack of infiltrating CD8+ T lymphocytes. Circular RNAs (circRNAs) are a novel type of prevalent noncoding RNA that have been implicated in tumorigenesis and progression, while their roles in modulating CD8+ T cells infiltration and immunotherapy in bladder cancer have not yet been investigated. Herein, we uncover circMGA as a tumor-suppressing circRNA triggering CD8+ T cells chemoattraction and boosting the immunotherapy efficacy. Mechanistically, circMGA functions to stabilize CCL5 mRNA by interacting with HNRNPL. In turn, HNRNPL increases the stability of circMGA, forming a feedback loop that enhances the function of circMGA/HNRNPL complex. Intriguingly, therapeutic synergy between circMGA and anti-PD-1 could significantly suppress xenograft bladder cancer growth. Taken together, the results demonstrate that circMGA/HNRNPL complex may be targetable for cancer immunotherapy and the study advances our understanding of the physiological roles of circRNAs in antitumor immunity.


Asunto(s)
Ribonucleoproteína Heterogénea-Nuclear Grupo L , Neoplasias de la Vejiga Urinaria , Humanos , Linfocitos T CD8-positivos , ARN Circular/genética , Inmunoterapia/métodos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Microambiente Tumoral/genética
18.
Int J Hyperthermia ; 40(1): 2182749, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36889694

RESUMEN

OBJECTIVE: To investigate the effects of standardized fluid management (SFM) on cardiac function in patients with pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: Patients with PMP who underwent CRS + HIPEC at our center were retrospectively analyzed. The patients were divided into control and study groups according to whether SFM was applied after CRS + HIPEC. We compared the preoperative and postoperative cardiac and renal function parameters, daily fluid volume three days after CRS, and cardiovascular-related adverse events. Univariate and multivariate analyses were performed to identify the indicators affecting clinical prognosis. RESULT: Among the 104 patients, 42 (40.4%) were in the control group and 62 (59.6%) in the study group. There were no statistically significant differences between the two groups in the main clinicopathological characteristics, preoperative cardiac and renal function parameters, and CRS + HIPEC-related indicators. The incidences of cardiac troponin I (CTNI) > upper limit of normal (ULN), >2 × ULN, >3 × ULN, serum creatinine > ULN, and blood urea nitrogen > ULN were higher in the control group than in the study group (p < 0.05). The median daily fluid volume of the control group was higher than that of the study group 3 days after CRS (p < 0.05). Postoperative CTNI > 2 × ULN was an independent risk factor for serious circulatory adverse events. Survival analysis revealed pathological grading, completeness of cytoreduction score, and postoperative CTNI > ULN as independent prognostic factors. CONCLUSIONS: SFM after CRS + HIPEC in patients with PMP may reduce cardiovascular adverse events risk and improve clinical outcomes.


Asunto(s)
Hipertermia Inducida , Neoplasias Peritoneales , Seudomixoma Peritoneal , Humanos , Seudomixoma Peritoneal/tratamiento farmacológico , Quimioterapia Intraperitoneal Hipertérmica , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Neoplasias Peritoneales/cirugía , Estudios de Casos y Controles , Estudios Retrospectivos , Resultado del Tratamiento , Hipertermia Inducida/efectos adversos , Terapia Combinada , Tasa de Supervivencia
19.
JAMA ; 329(8): 640-650, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36757755

RESUMEN

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Masculino , Activador de Tejido Plasminógeno , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Resultado del Tratamiento
20.
EBioMedicine ; 87: 104388, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36516610

RESUMEN

BACKGROUND: Brugada syndrome (BrS) is a severe inherited arrhythmia syndrome that can be unmasked by fever. METHODS: A multicentre clinical analysis was performed in 261 patients diagnosed with fever-induced BrS, including 198 (75.9%) and 27 (10.3%) patients who received next-generation genetic sequencing and epicardial arrhythmogenic substrate (AS) mapping, respectively. FINDINGS: In fever-induced BrS patients, pathogenic or likely pathogenic (P/LP) SCN5A variant carriers developed fever-induced BrS at a younger age, and more often in females and those of Caucasian descent. They exhibited significant electrophysical abnormalities, including a larger epicardial AS area, and more prolonged abnormal epicardial electrograms. During a median follow-up of 50.5 months (quartiles 32.5-81.5 months) after the diagnosis, major cardiac events (MCE) occurred in 27 (14.4%) patients. Patients with P/LP SCN5A variants had a higher ratio of MCE compared with the rest. Additionally, history of syncope, QRS duration, and Tpe interval could also predict an increased risk for future MCE according to univariate analysis. Multivariate analysis indicated that only P/LP SCN5A variants were independent significant predictors of MCE. Computational structural modelling showed that most variants are destabilizing, suggesting that Nav1.5 structure destabilization caused by SCN5A missense variants may contribute to fever-induced BrS. INTERPRETATION: In our cohort, P/LP SCN5A variant carriers with fever-induced BrS are more prevalent among patients of Caucasian descent, females, and younger patients. These patients exhibit aggressive electrophysiological abnormalities and worse outcome, which warrants closer monitoring and more urgent management of fever. FUNDING: The current work was supported by the National Natural Science Foundation Project of China (Nos. 82270332 & 81670304), The Fundamental Research Funds for the Central Universities of China - Independent Research Project of Wuhan University (No. 2042022kf1217) from China; the National Institutes of Health of USA [NIH R56 (HL47678), NIH R01 (HL138103), and NIH R01 (HL152201)], the W. W. Smith Charitable Trust and the Wistar and Martha Morris Fund, Sharpe-Strumia Research Foundation, the American Heart Association Postdoctoral Fellowship (20POST35220002) from United States; the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences (PREDICT2) from the Netherlands.


Asunto(s)
Síndrome de Brugada , Femenino , Estados Unidos , Humanos , Síndrome de Brugada/etiología , Síndrome de Brugada/genética , Arritmias Cardíacas/genética , Canal de Sodio Activado por Voltaje NAV1.5/genética , Mutación Missense
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