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Increased atmospheric nitrogen (N) deposition significantly disturbs ecosystem N cycle. Although foliar interception and uptake of N deposition can provide an important alternative N supply to forest ecosystems, the mechanisms regulating foliar N uptake from wet deposition are not fully understood. Here, we selected 19 woody species with a wide range of plant traits from different functional groups and conducted a 15N isotope labelling experiment through brushing 15NH4 + and 15NO3 - solution on canopy leaves. Our findings demonstrate that leaves can directly absorb N from wet deposition within a few hours. The average leaf 15N recoveries were 10% and 28% under 15NH4 + and 15NO3 - treatments across species, respectively, while twig N recoveries were only 1%-7% of leaf N recoveries. Differences in foliar N uptake efficiency among species were closely associated with leaf traits but were little influenced by meteorological conditions or soil nutrient status. Specifically, plants with higher leaf N concentration, larger specific leaf area and lower wax concentration exhibited higher leaf N recovery. Our results indicated that tree canopies could directly absorb N from atmospheric deposition. We highlight the critical role of leaf traits in determining canopy foliar N uptake, which may consequently influence plant competition under elevated N deposition.
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OBJECTIVE: Weight is an influential factor in knee osteoarthritis (KOA). However, the effect of abnormal body weight on chitosan's efficacy in treating KOA is unclear. This study aimed to explore the differences in the effectiveness of arthroscopic surgery combined with intra-articular chitosan injection for KOA in patients with abnormal body weight. METHODS: Patients with stage II-III KOA (Kellgren-Lawrence rating, K-L) undergoing arthroscopic surgery were recruited for this clinical study from January 2020 to September 2021. Based on body mass index (BMI) and intra-articular chitosan injection, patients with KOA undergoing arthroscopic surgery (138 patients) were divided into four groups: low-weight-non-injection (Lw-N, BMI <18.5); low-weight-chitosan injection (Lw-CS, BMI <18.5); overweight-non-injection (Ow-N, BMI ≥25); overweight-chitosan injection (Ow-CS, BMI ≥25). A 2-year follow-up was conducted to evaluate various indicators, including the visual analogue scale (VAS) and the Western Ontario and McMaster Universities osteoarthritis index score (WOMAC). Statistical analyses were performed using relevant parametric or non-parametric tests. RESULTS: In total, 138 patients with KOA were included in this study. There were no significant differences in gender, age, and incidence of chronic residual pain after arthroscopy among the four groups (p > 0.05). The proportion of patients undergoing subsequent knee arthroplasty during the 2-year follow-up period was significantly higher in the Ow-CS group (20/35) than in the Lw-CS group (12/39) (p < 0.05). The K-L rating showed an overall increasing trend over time, with the K-L rating in the Ow-N and Ow-CS groups significantly higher than that in the Lw-CS group at the final follow-up (p < 0.05). VAS and WOMAC scores significantly decreased at 1 and 3 months post-arthroscopy and then increased. One month after arthroscopy, VAS was significantly lower (p < 0.05) in the intra-articular chitosan injection groups (Lw-CS and Ow-CS) compared with the non-injection groups (Lw-N and Ow-N). VAS was lower in the Ow-CS group than in the Lw-CS group (p < 0.05). There was no significant difference in WOMAC between the intra-articular chitosan injection and non-injection groups at each time point (Lw-N vs. Lw-CS, Ow-N vs. Ow-CS, p > 0.05). CONCLUSION: Arthroscopic surgery combined with intra-articular chitosan injection shows short-term positive effects in treating KOA. Intra-articular chitosan injection appears to have a greater short-term pain relief effect in obese patients.
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Artroscopia , Quitosana , Osteoartrite do Joelho , Humanos , Quitosana/administração & dosagem , Osteoartrite do Joelho/cirurgia , Artroscopia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Injeções Intra-Articulares , Idoso , Medição da Dor , Índice de Massa Corporal , Terapia CombinadaRESUMO
BACKGROUND: This study aimed to investigate the clinical efficacy of intra-articular injections of medical chitosan for treating knee osteoarthritis (KOA) and measure the lipid metabolism profiles of the synovial tissue. METHODS: 60 patients with KOA undergoing conservative treatment were recruited and randomized into two groups: one without pharmacological intervention (OA group) and the other receiving course-based intra-articular medical chitosan injections (CSI group). Quantitative lipidomic profile of synovial tissue was analyzed. Functional scores, including Kellgren-Lawrence rating (K-L), VAS, WOMAC scoring, and AKS scoring were conducted. RESULTS: Survival from the initial conservative treatment to final knee arthroplasty was significantly longer in the CSI group compared to the OA group. Except for the pre-surgery VAS score, no statistically significant differences were observed in the other scores, including K-L, initial VAS, WOMAC, and AKS. However, the CSI group experienced a slightly more pronounced decline in AKS-Knee subscores compared to the OA group. Compared to the CSI group, the OA group exhibited a significant upregulation in most differential lipids, particularly triacylglycerides (TAGs, 77%). The OA group had notably higher levels of long-chain unsaturated fatty acids. CONCLUSION: Intra-articular injection of medical chitosan significantly prolongs the survival period before knee arthroplasty and reduces the deposition of TAGs metabolites.
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Thrombin is an important ischemia/reperfusion injury (IRI) mediator in patients with ST-elevation myocardial infarction (STEMI). This study examines the use of bivalirudin, a direct thrombin inhibitor, in reducing IRI in STEMI patients. STEMI patients (n = 21) were treated with bivalirudin and compared to 21 patients treated with unfractionated heparin (UFH) from the EARLY Assessment of Myocardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). Infarct size (IS) and left ventricular ejection fraction (LVEF) were comparable between the two groups at follow up. During the first cardiac magnetic resonance (CMR) scan within the first week after percutaneous coronary intervention (PCI), all patients in both the bivalirudin and UFH groups exhibited myocardial edema. However, the myocardium edema volume was significantly less in the bivalirudin group (p < 0.05). At the one-month follow-up, a smaller proportion of patients in the bivalirudin group than in the UFH group exhibited myocardial edema (4.7% vs. 33.3%, p < 0.05). At the three-month follow-up, myocardial edema had completely resolved in the bivalirudin group, while it persisted in two patients in the UFH group. The incidence and volume of microvascular obstruction (MVO) were significantly lower in the bivalirudin group during the acute phase. Additionally, the incidence of intramyocardial hemorrhage (IMH) was significantly lower in the bivalirudin group during both the acute and follow up (p < 0.05). These findings were corroborated by T2 and T1 mapping results. The study concluded that the use of bivalirudin for anticoagulation is associated with attenuated IRI in STEMI patients who receive primary PCI.
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BACKGROUND: The prognostic value of left ventricular segmental strain (SS) in ST-elevation myocardial infarction (STEMI) remains unclear. HYPOTHESIS: To assess the prognostic value and application of SS. STUDY TYPE: Retrospective analysis of a prospective registry. POPULATION: Five hundred and forty-four patients after STEMI (500 in Cohort 1, 44 in Cohort 2). FIELD STRENGTH/SEQUENCE: 3 T, balanced steady-state free precession, gradient echo, and gradient echo contrast-enhanced images. ASSESSMENT: Participants underwent cardiac MR during the acute phase after STEMI. Infarct-related artery (IRA) strain was determined based on SS obtained from cine images. The primary endpoint was the composite of major adverse cardiovascular events (MACEs) after 8 years of follow-up. In Cohort 2, SS stability was assessed by MR twice within 8 days. Contrast and non-contrast risk models based on SS were established, leading to the development of an algorithm. STATISTICAL TEST: Student's t-test, Mann-Whitney U-test, Cox and logistic regression, Kaplan-Meier analysis, net reclassification index (NRI). P < 0.05 was considered significant. RESULTS: During a median follow-up of 5.2 years, 83 patients from Cohort 1 experienced a MACE. Among SS, IRA peak circumferential strain (IRA-CS) was an independent factor for MACEs (adjusted hazard ratio 1.099), providing incremental prognostic value (NRI 0.180, P = 0.10). Patients with worse IRA-CS (>-8.64%) demonstrated a heightened susceptibility to MACE. Additionally, IRA-CS was significantly associated with microvascular obstruction (MVO) (adjusted odds ratio 1.084) and infarct size (r = 0.395). IRA-CS showed comparable prognostic effectiveness to global peak circumferential strain (NRI 0.100, P = 0.39), also counterbalancing contrast and non-contrast risk models (NRI 0.205, P = 0.05). In Cohort 2, IRA-CS demonstrated stability between two time points (P = 0.10). Based on risk models incorporating IRA-CS, algorithm "HJKL" was preliminarily proposed for stratification. DATA CONCLUSIONS: IRA-CS is an important prognostic factor, and an algorithm based on it is proposed for stratification. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.
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Osteoarthritis (OA) is a prevalent degenerative joint disease that significantly impacts individuals and healthcare systems worldwide. However, the exploration of N6-methyladenosine (m6A)-related aging genes in OA pathogenesis remains largely underexplored. This study aimed to elucidate the role of m6A-related aging genes in OA and to develop a robust diagnostic model based on their expression profiles. Leveraging publicly available gene expression datasets, we conducted consensus clustering to categorize OA into distinct subtypes, guided by the expression patterns of m6A-related aging genes. Utilizing XGBoost, a cutting-edge machine learning approach, we identified key diagnostic genes and constructed a predictive model. Our investigation extended to the immune functions of these genes, shedding light on potential therapeutic targets and underlying regulatory mechanisms. Our analysis unveiled specific OA subtypes, each marked by unique expression profiles of m6A-related aging genes. We pinpointed a set of pivotal diagnostic genes, offering potential therapeutic avenues. The developed diagnostic model exhibited exceptional capability in distinguishing OA patients from healthy controls. To corroborate our computational findings, we performed quantitative real-time polymerase chain reaction analyses on two cell lines: HC-OA (representing adult osteoarthritis cells) and C-28/I2 (representative of normal human chondrocytes). The gene expression patterns observed were consistent with our bioinformatics predictions, further validating our initial results. In conclusion, this study underscores the significance of m6A-related aging genes as promising biomarkers for diagnosis and prognosis, as well as potential therapeutic targets in OA. Although these findings are encouraging, further validation and functional analyses are crucial for their clinical application.
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Neoplasias , Osteoartrite , Adulto , Humanos , Adenina , Envelhecimento/genética , Osteoartrite/diagnóstico , Osteoartrite/genéticaRESUMO
BACKGROUND: The impact of left ventricular mechanical dyssynchrony (LVMD) on the long-term prognosis of ST-segment elevation myocardial infarction (STEMI) is unclear. HYPOTHESIS: MR uniformity ratio estimates (URE) can detect LVMD and assess STEMI prognosis. STUDY TYPE: Retrospective analysis of a prospective multicenter registry (EARLY-MYO trial, NCT03768453). POPULATION: Overall, 450 patients (50 females) with first-time STEMI were analyzed, as well as 40 participants without cardiovascular disease as controls. FIELD STRENGTH/SEQUENCE: 3.0-T, balanced steady-state free precession cine and late gadolinium enhancement imaging. ASSESSMENT: MRI data were acquired within 1 week of symptom onset. Major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal re-infarction, hospitalization for heart failure, and stroke, were the primary clinical outcomes. LVMD was represented by circumferential URE (CURE) and radial URE (RURE) calculated using strain measurements. The patients were grouped according to clinical outcomes or URE values. Patients' clinical characteristics and MR indicators were compared. STATISTICAL TESTS: The Student's t-test, Mann-Whitney U test, chi-square test, Fisher's exact test, receiver operating characteristic curve analysis with area under the curve, Kaplan-Meier analysis, Cox regression, logistic regression, intraclass correlation coefficient, c-index, and integrated discrimination improvement were used. P < 0.05 was considered statistically significant. RESULTS: CURE and RURE were significantly lower in patients with STEMI than in controls. The median follow-up was 60.5 months. Patients with both lower CURE and RURE values experienced a significantly higher incidence of MACEs by 3.525-fold. Both CURE and RURE were independent risk factors for MACEs. The addition of UREs improved diagnostic efficacy and risk stratification based on infarct size and left ventricular ejection fraction (LVEF). The indicators associated with LVMD included male sex, serum biomarkers (peak creatine phosphokinase and cardiac troponin I), infarct size, and LVEF. DATA CONCLUSION: CURE and RURE may be useful to evaluate long-term prognosis after STEMI. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
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Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Feminino , Humanos , Masculino , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Volume Sistólico , Função Ventricular Esquerda , Estudos Prospectivos , Meios de Contraste , Estudos Retrospectivos , Gadolínio , Imageamento por Ressonância Magnética/métodos , Prognóstico , Intervenção Coronária Percutânea/efeitos adversos , Imagem Cinética por Ressonância Magnética/métodosRESUMO
BACKGROUND: Polycystic kidney disease is the most common hereditary kidney disorder with early and frequent hypertension symptoms. The mechanisms of cyst progression in polycystic kidney disease remain incompletely understood. METHODS: Bsg (basigin) heterozygous and homozygous knockout mice were generated using cas9 system, and Bsg overexpression was achieved by adeno-associated virus serotype 9 injection. Renal morphology was investigated through histological and imaging analysis. Molecular analysis was performed through transcriptomic profiling and biochemical approaches. RESULTS: Bsg-deficient mice exhibited significantly elevated arterial blood pressure. Further investigation demonstrated that Bsg deficiency triggers spontaneous cystic formation in mouse kidneys, which shares similar cyst pathological features and common transcriptional regulatory pathways with human polycystic kidney disease. Moreover, Bsg disruption promoted polycystin-1 ubiquitination and degradation, leading to activation of polycystic kidney disease associated cAMP and AMPK signaling pathways in Bsg knockout mouse kidneys. Finally, adeno-associated virus serotype 9 mediated Bsg reexpression reversed cystic progression in Bsg knockout mice in vivo, and Bsg overexpression inhibited the expansion of Madin-Darby canine kidney cysts in vitro. CONCLUSIONS: Our findings show that Bsg deficiency leads to an early-onset spontaneous polycystic kidney phenotype, suggesting that dysregulated Bsg signaling may be a contributing factor in cystogenesis.
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Cistos , Doenças Renais Policísticas , Animais , Cães , Humanos , Camundongos , Basigina/genética , Basigina/metabolismo , Cistos/metabolismo , Cistos/patologia , Rim/metabolismo , Camundongos Knockout , Doenças Renais Policísticas/genética , Doenças Renais Policísticas/metabolismoRESUMO
Background: Acute myocardial infarction (AMI) poses a significant threat to cardiovascular diseases (CVDs), leading to a high risk of heart failure (HF) and cardiovascular death. Growing evidence has unveiled the potential of sodium-glucose cotransporter-2 (SGLT2) inhibitors to improve cardiovascular outcomes in patients with CVD regardless of diabetes, but there is limited evidence in AMI patients. Furthermore, it is controversial whether the effects can be ascribed to the amelioration of left ventricular (LV) function, which further complicates the understanding of their underlying mechanism. Methods: This study is a prospective, phase IV, open-label, parallel group, single-center trial conducted in a large tertiary teaching hospital in China. A total of 120 patients with AMI and type 2 diabetes mellitus (T2DM) will be included. Those who received SGLT2 inhibitors are considered as the experimental group, and those taking other antidiabetic agents are considered as the control group. The primary outcome is change in LV end-systolic volume index (LVESVi) measured by cardiac magnetic resonance (CMR) imaging from baseline during 1-year follow-up period. Secondary outcomes include other LV parameters such as LV mass, LV volume, and LV ejection fraction (EF); quality of life and functional capacity such as Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OS) and EuroQol-5 dimension (EQ-5D); biomarkers associated with diagnostic parameters of AMI and possible mechanisms on cardiovascular protection, such as creatine kinase, troponin T (TnT) level, troponin I (TnI) level, soluble suppression of tumorigenicity-2 (sST2), galectin-3 (Gal-3), fibroblast growth factor 21 (FGF21), and microRNA (miRNA) level. Discussion: This study aims to investigate whether SGLT2 inhibitors could improve LV function by measuring CMR, quality of life, and functional capacity in patients with AMI in real-world settings, providing evidence on the underlying mechanism of SGLT2 inhibitors on cardioprotection. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=173672, identifier ChiCTR2200065792.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Estudos Prospectivos , Qualidade de Vida , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.
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Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Coração , Imageamento por Ressonância Magnética , Função Ventricular Esquerda , Volume Sistólico , Remodelação Ventricular , Valor Preditivo dos TestesRESUMO
PURPOSE: The purpose of this study was to predict the probability of postoperative pulmonary infection in elderly patients with hip fractures by developing and validating a precise model. METHODS: The clinical data of 1008 elderly hip fracture patients undergoing surgical treatment in Shanghai Tenth Peoples' Hospital were retrospectively selected. A univariate analysis and multivariate regression were used to analyze the independent risk factors for postoperative pulmonary infection in elderly patients with hip fractures. A risk prediction model was established, and a nomogram was drawn. The area under the ROC curve and HosmerâLemeshow test were used to evaluate the predictive effect of the model. RESULTS: The multivariate regression analysis indicated that age > 73, time from fracture to surgery (d) > 4 days, smoking, ASA ≥ III level, COPD, hypoproteinemia, red cell distribution width > 14.8%, mechanical ventilation time > 180 min, and stay in the ICU were independent risk factors for postoperative pulmonary infection in elderly patients. The AUCs of the model were 0.891 and 0.881, 0.843, respectively, in the two verification groups. For the HosmerâLemeshow test, the P values were 0.726 in the modeling group and 0.497 and 0.231 in the verification group (P > 0.05). CONCLUSION: Overall, this study uncovered different independent risk factors for postoperative pulmonary infection in patients with hip fractures. The nomogram can effectively predict the occurrence of postoperative pulmonary infection.
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Fraturas do Quadril , Pneumonia , Humanos , Idoso , Nomogramas , Estudos Retrospectivos , China , Fraturas do Quadril/cirurgia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
BACKGROUND: Evaluation of cardiac injuries is essential in patients with ST-elevation myocardial infarction (STEMI). Cardiac magnetic resonance (CMR) has become the gold standard for quantifying cardiac injuries; however, its routine application is limited. A nomogram is a useful tool for prognostic prediction based on the comprehensive utilization of clinical data. We presumed that the nomogram models established using CMR as a reference could precisely predict cardiac injuries. METHODS: This analysis included 584 patients with acute STEMI from a CMR registry study for STEMI (NCT03768453). The patients were divided into training (n = 408) and testing (n = 176) datasets. The least absolute shrinkage and selection operator method and multivariate logistic regression were used to construct nomograms for predicting left ventricular ejection fraction (LVEF) ≤40%, infarction size (IS) ≥ 20% on the LV mass, and microvascular dysfunction. RESULTS: The nomogram for predicting LVEF≤40%, IS≥20%, and microvascular dysfunction comprised 14, 10, and 15 predictors, respectively. With the nomograms, the individual risk probability of developing specific outcomes could be calculated, and the weight of each risk factor was demonstrated. The C-index of the nomograms in the training dataset were 0.901, 0.831, and 0.814, respectively, and were comparable in the testing set, showing good nomogram discrimination and calibration. The decision curve analysis demonstrated good clinical effectiveness. Online calculators were also constructed. CONCLUSIONS: With the CMR results as the reference standard, the established nomograms demonstrated good effectiveness in predicting cardiac injuries after STEMI and could provide physicians with a new option for individual risk stratification.
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Traumatismos Cardíacos , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Nomogramas , Volume Sistólico , Função Ventricular Esquerda , Espectroscopia de Ressonância Magnética , Imagem Cinética por Ressonância Magnética/métodos , Valor Preditivo dos TestesRESUMO
Background: Total knee arthroplasty is currently a reliable treatment for end-stage knee osteoarthritis. However, chronic postsurgical pain (CPSP) is substantially thought to reduce patient satisfaction. NSAID-based oral analgesics were used to manage CPSP, but research on the duration of postoperative analgesic use (DAU) and prolonged analgesic use (PAU) are presently scarce. Methods: Preoperative, perioperative, and one-year or above postoperative follow-up data were collected from 162 patients who underwent total knee arthroplasty between 1 June 2018 and 1 March 2019, and the DAU and the discontinuation time of each patient after discharge were recorded. Observational statistical analysis, diagnostic test, and predictive nomogram construction were performed on the collected data. Results: The 3-month DAU has good diagnostic utility for poor outcome of postoperative months twelve (POM12). The constructed nomogram shows that gender, preoperative Numeric Rating Scale (NRS) movement pain scores, duration of surgery, postoperative days three (POD3) moderate to severe movement pain, and POD3 pain rescue medication were significant prognostic predictors of PAU after discharge. The area under the curve (AUC) of the 3-month, 6-month, and 12-month nomogram receiver operating characteristic (ROC) curves were calculated to be 0.741, 0.736, and 0.781. Conclusion: PAU was defined as more than three months of NSAID-based oral analgesic use after TKA. Prognostic predictors of PAU after TKA were identified, and visualized nomogram was plotted and evaluated. The evaluation indicated that the prediction model had the good predictive ability and was a valuable tool for predicting PAU after discharge.
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BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) provides an alternative for poor candidates for long-term oral anticoagulation (OAC). To prevent device-related thrombosis (DRT), OAC should be continued for the first 45 days to allow complete endothelialization post-LAAO implantation. Whereas, evidence is limited on the feasibility and safety of direct oral anticoagulants (DOACs) used after LAAO. METHODS: This was a retrospective observational single-center study of AF patients undergoing LAAO with a Watchman device and receiving either low-dose dabigatran (110mg twice daily) or warfarin in the peri- and post-procedural period for 45 days. Transesophageal echocardiography was scheduled to perform at 6 weeks, 6 months, and 12 months after the procedure to assess the stability of the device and to detect DRT. Incidence of thromboembolic and bleeding events were also evaluated during the follow-up period. RESULTS: There were a total of 84 patients who successfully underwent Watchman implantation, with 38 patients (45.2%) receiving low-dose dabigatran and 46 patients (54.8%) using warfarin post-LAAO. Peri-procedural complications occurred in 10 patients, with 3 patients in the dabigatran group and 7 patients in the warfarin group (7.9% vs. 15.2%, p = 0.30). During the 12-month follow-up, 1 patient experienced major bleeding and 16 patients suffered minor bleeding in the warfarin group, while 5 patients treated with dabigatran had minor bleeding (34.8% vs. 13.2%, p = 0.02). Besides, 6 DRT (15.8%) were detected in dabigatran groups, and the incidence was higher than in the warfarin group (15.8% vs. 2.2%, p = 0.03). No DRT-related ischemic events were found. CONCLUSIONS: This study suggested that short-term low-dose dabigatran (110â mg twice daily) could significantly decrease the risk of bleeding compared with warfarin at the expense of increased risk of DRT post-LAAO. Therefore, low-dose dabigatran should be used with caution for post-implant anticoagulation of LAAO. Further studies are urgently needed on the feasibility and safety of DOACs post-LAAO.
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Apêndice Atrial , Fibrilação Atrial , Trombose , Anticoagulantes/efeitos adversos , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/complicações , Humanos , Resultado do Tratamento , Varfarina/efeitos adversosRESUMO
BACKGROUND: Shift work is associated with increased risk of acute myocardial infarction (AMI) and worsened prognosis. However, the mechanisms linking shift work and worsened prognosis in AMI remain unclear. OBJECTIVES: This study sought to investigate the impact of shift work on reperfusion injury, a major determinant of clinical outcomes in AMI. METHODS: Study patient data were obtained from the database of the EARLY-MYO-CMR (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI) registry, which was a prospective, multicenter registry of patients with ST-segment elevation myocardial infarction (STEMI) undergoing cardiac magnetic resonance (CMR) imaging after reperfusion therapy. The primary endpoint was CMR-defined post-reperfusion infarct size. A secondary clinical endpoint was the composite of major adverse cardiac events (MACE) during follow-up. Potential mechanisms were explored with the use of preclinical animal AMI models. RESULTS: Of 706 patients enrolled in the EARLY-MYO-CMR registry, 412 patients with STEMI were ultimately included. Shift work was associated with increased CMR-defined infarct size (ß = 5.94%; 95% CI: 2.94-8.94; P < 0.0001). During a median follow-up of 5.0 years, shift work was associated with increased risks of MACE (adjusted HR: 1.92; 95% CI: 1.12-3.29; P = 0.017). Consistent with clinical findings, shift work simulation in mice and sheep significantly augmented reperfusion injury in AMI. Mechanism studies identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that played a crucial role in mediating the detrimental effects of shift work on myocardial injury. CONCLUSIONS: The current study provided novel findings that shift work increases myocardial infarction reperfusion injury. It identified a novel nuclear receptor subfamily 1 group D member 1/cardiotrophin-like cytokine factor 1 axis in the heart that might play a crucial role in mediating this process. (Early Assessment of Myocardial Tissue Characteristics by CMR in STEMI [EARLY-MYO-CMR] registry; NCT03768453).
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Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Infarto do Miocárdio com Supradesnível do Segmento ST , Jornada de Trabalho em Turnos , Animais , Ritmo Circadiano , Humanos , Imagem Cinética por Ressonância Magnética , Camundongos , Infarto do Miocárdio/terapia , Estudos Prospectivos , Receptores Citoplasmáticos e Nucleares , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , OvinosRESUMO
BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a multifactorial disease, and agnogenic ONFH, otherwise known as idiopathic ONFH, is rare in clinic. Idiopathic ONFH that exhibits severe necrosis and progresses extremely rapidly is called rapidly destructive hip disease (RDHD). RDHD greatly affects patients but is rarely reported in clinical practice and literature. CASE PRESENTATION: In this study, a 64-year-old male patient with complete collapse and necrosis of the right femoral head complicated with severe bone destruction at 10 months after left total hip arthroplasty (THA) was reported. The period from the intact structure of the right femoral head to the first discovery of its complete collapse, according to imaging results, was 7 months. The duration from the occurrence of symptoms in the right hip joint to the first discovery of complete collapse and necrosis of the femoral head was only 5 months. At present, the cause has not been determined based on medical history, symptoms, signs, imaging evaluation results, laboratory examination results, and pathological examination results, though it has been identified as severe idiopathic aseptic necrosis of the femoral head with rapid progression, or RDHD. Finally, right THA was performed, and a good outcome was observed in the patient at present. CONCLUSIONS: As a rare hip joint disease, RDHD greatly influences the normal life of patients. RDHD of the contralateral side after unilateral THA is even scarcer. Left THA may be one of the important factors accelerating the necrosis of the right femoral head. Hopefully, with this case report, more attention will be paid to the contralateral hip joint in patients undergoing unilateral THA by clinicians and rehabilitation physicians, and a clinical reference will be provided for the research on RDHD.
Assuntos
Artroplastia de Quadril , Necrose da Cabeça do Fêmur , Osteoartrite do Quadril , Artroplastia de Quadril/métodos , Cabeça do Fêmur/cirurgia , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/cirurgia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Full-dose prednisone (FP) regimen in the treatment of high-risk immunoglobulin A nephropathy (IgAN) patients, is still controversial. The pulsed intravenous methylprednisolone combined with alternative low-dose prednisone (MCALP) might have a more favorable safety profile, which has not been fully investigated. Eighty-seven biopsy-proven IgAN adult patients and proteinuria between 1 and 3.5 g/24 h after ACEI/ARB for at least 90 days were randomly assigned to 6-month therapy: (1) MCALP group: 0.5 g of methylprednisolone intravenously for three consecutive days at the beginning of the course and 3rd month respectively, oral prednisone at a dose of 15 mg every other day for 6 months. (2) FP group: 0.8-1.0 mg/kg/days of prednisone (maximum 70 mg/day) for 2 months, then tapered by 5 mg every 10 days for the next 4 months. All patients were followed up for another 12 months. The primary outcome was complete remission (CR) of proteinuria at 12 months. The percentage of CR at 12th and 18th month were similar in the MCALP and FP groups (51% vs 58%, P = 0.490, at 12th month; 60% vs 56%, P = 0.714, at 18th month). The cumulative dosages of glucocorticoid were less in the MCALP group than FP group (4.31 ± 0.26 g vs 7.34 ± 1.21 g, P < 0.001). The analysis of the correlation between kidney biopsy Oxford MEST-C scores with clinical outcomes indicated the percentages of total remission was similar between two groups with or without M1, E1, S1, T1/T2, and C1/C2. More patients in the FP group presented infections (8% in MCALP vs 21% in FP), weight gain (4% in MCALP vs 19% in FP) and Cushing syndrome (3% in MCALP vs 18% in FP). These data indicated that MCALP maybe one of the choices for IgAN patients with a high risk for progression into ESKD.Trial registration: The study approved by the Chinese Clinical Trial Registry (registration date 13/01/2018, approval number ChiCTR1800014442, https://www.chictr.org.cn/ ).
Assuntos
Glomerulonefrite por IGA/tratamento farmacológico , Glucocorticoides/administração & dosagem , Metilprednisolona/administração & dosagem , Prednisona/administração & dosagem , Proteinúria/tratamento farmacológico , Administração Intravenosa , Administração Oral , Adulto , Progressão da Doença , Redução da Medicação , Quimioterapia Combinada , Feminino , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/imunologia , Glucocorticoides/efeitos adversos , Humanos , Falência Renal Crônica/imunologia , Falência Renal Crônica/prevenção & controle , Masculino , Metilprednisolona/efeitos adversos , Prednisona/efeitos adversos , Estudos Prospectivos , Proteinúria/diagnóstico , Proteinúria/imunologia , Pulsoterapia , Indução de Remissão , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
CD147, also known as EMMPRIN or basigin, is a transmembrane glycoprotein receptor that activates matrix metalloproteinases and promotes inflammation. CD147 function is regulated by posttranslational modifications of which glycosylation has attracted the most attention. In this study, we demonstrated that glycosylated CD147 was the dominant form in heart tissue, and its levels were markedly elevated in response to transverse aortic constriction (TAC). Adeno-associated virus 9-mediated, cardiac-specific overexpression of wild-type CD147 in mice significantly promoted pressure overload-induced pathological cardiac remodeling accompanied by augmented oxidative stress and ferroptosis. By contrast, mutations of CD147 glycosylation sites notably weakened these detrimental effects of CD147. Mechanistically, CD147 exacerbated TAC-induced pathological cardiac remodeling via direct binding with the adaptor molecule TRAF2 and subsequent activation of TAK1 signalling, which was dependent on glycosylation of CD147. Collectively, our findings provide the first evidence that CD147 promoted pathological cardiac remodeling and dysfunction in a glycosylation-dependent manner through binding the adaptor protein TRAF2 and activating the downstream TRAF2-TAK1 signalling pathway. Thus, glycosylation of CD147 may be a potent interventional target for heart failure treatment.
Assuntos
Basigina/efeitos adversos , Cardiomegalia/fisiopatologia , Animais , Glicosilação , Humanos , Masculino , CamundongosRESUMO
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowered the risk of cardiovascular events in patients with diabetes or heart failure (HF) with reduced ejection fraction, whether they directly promote cardiac function remains unclear. Therefore, we sought to determine whether SGLT2 inhibitors could improve left ventricular (LV) function in these patients. METHODS: A literature search was conducted using MEDLINE, EMBASE, and Cochrane Library databases from their inception to July 9, 2021. Randomized clinical trials and cohort studies that reported LV function-related variables were included. RESULTS: Thirteen studies comprising 1437 patients (830 SGLT2 inhibitor-treated and 607 non-SGLT2 inhibitor-treated patients) and representing 7 randomized controlled trials with 640 individuals and 6 cohort studies with 797 individuals were included in this meta-analysis. LV regression [LV mass (LVM)], LV ejection fractions (LVEF), LV volumes [LV end-diastolic volumes and systolic volumes (LVEDV and LVESV, respectively], and LV diastolic function [mitral inflow E velocity to tissue Doppler e' ratio, E/e' and left atrial volume index (LAVI)] were all significantly improved in patients treated with SGLT2 inhibitors (weighted mean differences, 95% CI, LVM: -6.319 g, -10.850 to -1.789; LVEF: 2.458%, 0.693 to 4.224; LVEDV: -9.134 mL, -15.808 to -2.460; LVESV: -8.440 mL, -15.093 to -1.787; LAVI: -2.791 mL/m2, -.554 to -1.027; E/e': -1.567, -2.440 to -0.698). Subgroup analysis further confirmed the improvement of LV function mainly in patients with HF or those receiving empagliflozin treatment. CONCLUSIONS: Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment).