RESUMEN

Background: Deposition of adipose tissue may have a promoting role in the development of diabetic complications. This study is aimed at investigating the relationship between adipose tissue thickness and risk of contrast-induced nephropathy (CIN) in patients with Type 2 diabetes mellitus (T2DM). Methods: A total of 603 T2DM patients undergoing percutaneous coronary angiography or angioplasty with suspicious or confirmed stable coronary artery disease were enrolled in this study. The thicknesses of perirenal fat (PRF), subcutaneous fat (SCF), intraperitoneal fat (IPF), and epicardial fat (ECF) were measured by color Doppler ultrasound, respectively. The association of various adipose tissues with CIN was analyzed. Results: Seventy-seven patients (12.8%) developed CIN in this cohort. Patients who developed CIN had significantly thicker PRF (13.7 ± 4.0 mm vs. 8.9 ± 3.6 mm, p < 0.001), slightly thicker IPF (p = 0.046), and similar thicknesses of SCF (p = 0.782) and ECF (p = 0.749) compared to those who did not develop CIN. Correlation analysis showed that only PRF was positively associated with postoperation maximal serum creatinine (sCr) (r = 0.18, p = 0.012), maximal absolute change in sCr (r = 0.33, p < 0.001), and maximal percentage of change in sCr (r = 0.36, p < 0.001). In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of PRF (0.809) for CIN was significantly higher than those of SCF (0.490), IPF (0.594), and ECF (0.512). Multivariate logistic regression analysis further confirmed that thickness of PRF, rather than other adipose tissues, was independently associated with the development of CIN after adjusted for confounding factors (odds ratio (OR) = 1.53, 95% CI: 1.38-1.71, p < 0.001). Conclusions: PRF is independently associated with the development of CIN in T2DM patients undergoing coronary catheterization.

Asunto(s)

Medios de Contraste , Angiografía Coronaria , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Medios de Contraste/efectos adversos , Persona de Mediana Edad , Anciano , Angiografía Coronaria/efectos adversos , Factores de Riesgo , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tejido Adiposo/diagnóstico por imagen , Tejido Adiposo/patología , Enfermedades Renales/inducido químicamente , Grasa Intraabdominal/diagnóstico por imagen , Cateterismo Cardíaco/efectos adversos , Creatinina/sangre

RESUMEN

BACKGROUND: Atrial fibrillation (AF) is common among intensive care unit (ICU) patients and significantly raises the in-hospital mortality rate. Existing scoring systems or models have limited predictive capabilities for AF patients in ICU. Our study developed and validated machine learning models to predict the risk of in-hospital mortality in ICU patients with AF. METHODS AND RESULTS: Medical Information Mart for Intensive Care (MIMIC)-IV dataset and eICU Collaborative Research Database (eICU-CRD) were analyzed. Among ten classifiers compared, adaptive boosting (AdaBoost) showed better performance in predicting all-cause mortality in AF patients. A compact model with 15 features was developed and validated. Both the all variable and compact models exhibited excellent performance with area under the receiver operating characteristic curves (AUCs) of 1(95%confidence interval [CI]: 1.0-1.0) in the training set. In the MIMIC-IV testing set, the AUCs of the all variable and compact models were 0.978 (95% CI: 0.973-0.982) and 0.977 (95% CI: 0.972-0.982), respectively. In the external validation set, the AUCs of all variable and compact models were 0.825 (95% CI: 0.815-0.834) and 0.807 (95% CI: 0.796-0.817), respectively. CONCLUSION: An AdaBoost-based predictive model was subjected to internal and external validation, highlighting its strong predictive capacity for assessing the risk of in-hospital mortality in ICU patients with AF.

Asunto(s)

Fibrilación Atrial , Simulación por Computador , Mortalidad Hospitalaria , Aprendizaje Automático , Medición de Riesgo , Enfermedad Crítica , Fibrilación Atrial/mortalidad , Medición de Riesgo/métodos , Reproducibilidad de los Resultados , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años

RESUMEN

BACKGROUND: The triglyceride-glucose (TyG) index has demonstrated correlations with adverse clinical outcomes in patients with ischaemic stroke, coronary heart disease and cardiac failure. However, its association with overall mortality in individuals concurrently experiencing heart failure (HF) and chronic kidney disease (CKD) remains inadequately explored. METHODS: Utilizing the Medical Information Mart for Intensive Care IV (Version 2.2) repository, subjects underwent quartile stratification based on the TyG index. The primary endpoint was all-cause mortality during hospitalization. Cox proportional hazard models were employed to examine the correlation between TyG and all-cause mortality in HF patients with CKD. Evaluation involved Kaplan-Meier (KM) analysis and restricted cubic splines (RCSs) to compare mortality rates during hospitalization and 1 year after admission across cohorts with varying TyG index levels. RESULTS: A cohort of 1537 HF and CKD patients participated. Cox regression analysis revealed elevated TyG levels as an independent risk factor for both in-hospital and 1 year mortality. RCS analysis indicated a rising, non-linear association between TyG levels and all-cause mortality (P value for non-linear <0.001). KM survival curves demonstrated a statistically significant reduction in survival rates within the high TyG index group compared with the low one (log-rank P < 0.001). CONCLUSIONS: The TyG index exhibited substantial independent prognostic value for elevated in-hospital and 1 year all-cause mortality among the cohort with HF and CKD. These findings suggest that assessing the TyG index could play a crucial role in developing novel therapeutic strategies to improve outcomes for this high-risk demographic.

RESUMEN

Dysfunction of the sympathetic nervous system and increased epicardial adipose tissue (EAT) have been independently associated with the occurrence of cardiac arrhythmia. However, their exact roles in triggering arrhythmia remain elusive. Here, using an in vitro coculture system with sympathetic neurons, cardiomyocytes, and adipocytes, we show that adipocyte-derived leptin activates sympathetic neurons and increases the release of neuropeptide Y (NPY), which in turn triggers arrhythmia in cardiomyocytes by interacting with the Y1 receptor (Y1R) and subsequently enhancing the activity of the Na+/Ca2+ exchanger (NCX) and calcium/calmodulin-dependent protein kinase II (CaMKII). The arrhythmic phenotype can be partially blocked by a leptin neutralizing antibody or an inhibitor of Y1R, NCX, or CaMKII. Moreover, increased EAT thickness and leptin/NPY blood levels are detected in atrial fibrillation patients compared with the control group. Our study provides robust evidence that the adipose-neural axis contributes to arrhythmogenesis and represents a potential target for treating arrhythmia.

Asunto(s)

Adipocitos , Tejido Adiposo , Arritmias Cardíacas , Leptina , Miocitos Cardíacos , Neuropéptido Y , Pericardio , Humanos , Animales , Pericardio/metabolismo , Pericardio/patología , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Neuropéptido Y/metabolismo , Leptina/metabolismo , Adipocitos/metabolismo , Masculino , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Neuronas/metabolismo , Neuronas/patología , Intercambiador de Sodio-Calcio/metabolismo , Femenino , Receptores de Neuropéptido Y/metabolismo , Persona de Mediana Edad , Fibrilación Atrial/metabolismo , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/patología , Sistema Nervioso Simpático/metabolismo , Ratones , Tejido Adiposo Epicárdico

RESUMEN

BACKGROUND: The association between the lactate/albumin ratio (L/A) as a diagnostic indicator and unfavourable clinical outcomes has been established in patients with community-acquired pneumonia, sepsis and heart failure, but the connection between L/A and all-cause mortality in patients with acute myocardial infarction (AMI) has yet to be fully understood. METHODS: This was a retrospective cohort study using MIMIC-IV (v2.2) data, with 2816 patients enrolled and all-cause mortality during hospitalization as the primary outcome. Kaplan-Meier (KM) analysis was used to compare the all-cause mortality between high-level and low-level L/A groups. Receiver operating characteristic (ROC) curve, Restricted cubic splines (RCS) and Cox proportional hazards analysis were performed to investigate the relationship between L/A ratio and in-hospital all-cause mortality. RESULTS: L/A values were significantly higher in the non-survivor groups than the survival groups (1.14 [.20] vs. .60 [.36], p < .05), and area under the ROC curve [.734 (95% confidence interval, .694-.775)] was better than other indicators. Data of COX regression analysis showed that higher L/A value supposed to be an independent risk factor for in-hospital mortality. RCS analysis showed evidence of an increasing trend and a non-linear relationship between L/A and in-hospital mortality (p-value was non-linear <.05). KM survival curves were significantly lower in the high L/A group than the low L/A group (p < .001), and the former group had an increased risk of in-hospital mortality compared with the latter one (Log Rank p < .001). CONCLUSIONS: L/A demonstrates significant independent predictive power for elevated all-cause mortality during hospitalization in patients diagnosed with AMI.

Asunto(s)

Ácido Láctico , Infarto del Miocardio , Humanos , Estudios Retrospectivos , Pronóstico , Albúminas , Curva ROC

RESUMEN

At present, multiple myeloma (MM) is still an essentially incurable hematologic malignancy. Although BCMA-targeted therapies have achieved remarkable results, BCMA levels were found to be downregulated in patients with MM who relapsed after these treatments. Therefore, the search for other antigens specific to MM has become a priority. Independently of BCMA expression, G-protein-coupled receptor family C group 5 member D (GPRC5D) is mainly expressed in the plasma cells of MM patients, while it is expressed in a limited number of normal tissues. Combining MM-specific antigen GPRC5D and T-cell-mediated therapies would be a promising therapeutic strategy for MM. Recently, we constructed a new anti-GPRC5D × anti-CD3 T-cell-engaging bispecific antibody (TCB), BR109, which was capable of binding to human GPRC5D and human CD3ε. Moreover, BR109 was proven to have relatively good stability and antitumor activity. BR109 could specifically trigger T-cell-mediated cytotoxicity against many GPRC5D-positive MM cells in vitro. Meanwhile, antitumor activity was demonstrated in MM cell line xenograft mouse models with human immune cell reconstitution. These preclinical studies have formed a solid foundation for the evaluation of MM treatment efficacy in clinical trials.

RESUMEN

INTRODUCTION: Percutaneous coronary intervention (PCI)-related myocardial infarction (type 4a MI) and major periprocedural myocardial injury have been demonstrated leading to poor prognosis of patients with coronary heart disease (CHD) undergoing elective PCI and still remain high occurrence even after the therapy of dual antiplatelet agents and statins. Proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to be effectively in reducing the risk of acute MI (AMI). However, the effect of alirocumab on preventing PCI-related MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI remains uncertain. METHODS AND ANALYSIS: Alirocumab effect on Preventing Periprocedural ischaemic Events in coronary heart diseAse patients undergoing coronary StEnting trial is a multicentre, open-label, randomised controlled trial aiming to determine whether alirocumab could reduce the incidence of type 4a MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI. In total, 422 non-AMI CHD patients planned to undergo elective PCI will be randomly assigned to receive standard pharmacotherapy of CHD (control group) or additional use of subcutaneous alirocumab 75 mg 1 day before procedure (alirocumab group). The primary outcome is type 4a MI or major periprocedural myocardial injury defined as high-sensitivity cardiac troponin elevating above 5×99 th percentile upper reference limit in 48 hours after PCI. Patients will continue receiving standard pharmacotherapy or additional biweekly subcutaneous alirocumab 75 mg for 3 months according to the initial randomisation group. We will follow up for 3 months and record all the major adverse cardiovascular events (MACEs). Incidence of PCI-related MI or major periprocedural myocardial injury, and MACE in 3 months after PCI will be compared between control group and alirocumab group. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University with approval number: (2022)02-140-01. The results of this study will be reported through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200063191.

Asunto(s)

Enfermedad Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto

RESUMEN

Background: The disruption of white matter (WM) integrity is related to poststroke cognitive impairment (PSCI). The exploration of WM integrity alterations in the chronic stage of acute ischemic stroke (AIS) may help to improve the long-term outcomes of PSCI. Methods: Sixty patients showing impaired cognitive functions within 3 days after AIS (baseline) and 25 healthy controls underwent diffusion kurtosis imaging scan and cognitive assessment at baseline and 1 year. Based on the tract-based spatial statistics (TBSS), kurtosis fractional anisotropy (KFA) and mean kurtosis (MK) were compared in WM tracts between the groups. Results: One year after AIS, 25 patients were diagnosed with PSCI and 35 patients with non-cognitive impairment (NCI). Compared with baseline, cognitive performance improved in 54 patients and remained unchanged in 6 patients at 1 year. TBSS analysis showed that there were no significant differences in WM tract integrity between the AIS and control groups at baseline (P > 0.05). Compared with the control group, the KFA and MK in multiple WM tracts in the AIS group decreased significantly at 1 year (P < 0.05). Longitudinal analysis showed that the KFA and MK of multiple WM tracts recorded at 1 year were significantly lower than those recorded at baseline in the AIS, PSCI, and NCI groups (P < 0.05), and PSCI group had a faster degeneration than NCI group (P < 0.05). Conclusion: The finding suggests that the patients with baseline impaired cognitive functions still have WM microstructural damages at 1 year poststroke, even if their cognitive function has improved or returned to normal. Cautions should be taken against the possible negative impact of these changes on long-term cognition.

Asunto(s)

Disfunción Cognitiva , Accidente Cerebrovascular Isquémico , Sustancia Blanca , Humanos , Sustancia Blanca/diagnóstico por imagen , Cognición , Imagen de Difusión Tensora/métodos , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología

RESUMEN

Treating and preventing infections by antimicrobial-resistant bacterial pathogens is a worldwide problem. Pathogens such as Staphylococcus aureus produce an array of virulence determinants, making it difficult to identify single targets for the development of vaccines or monoclonal therapies. We described a human-derived anti-S. aureus monoclonal antibody (mAb)-centyrin fusion protein ("mAbtyrin") that simultaneously targets multiple bacterial adhesins, resists proteolysis by bacterial protease GluV8, avoids Fc engagement by S. aureus IgG-binding proteins SpA and Sbi, and neutralizes pore-forming leukocidins via fusion with anti-toxin centyrins, while maintaining Fc- and complement-mediated functions. Compared with the parental mAb, mAbtyrin protected human phagocytes and boosted phagocyte-mediated killing. The mAbtyrin also reduced pathology, reduced bacterial burden, and protected from different types of infections in preclinical animal models. Finally, mAbtyrin synergized with vancomycin, enhancing pathogen clearance in an animal model of bacteremia. Altogether, these data establish the potential of multivalent mAbs for treating and preventing S. aureus diseases.

Asunto(s)

Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Animales , Humanos , Staphylococcus aureus , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/prevención & control , Infecciones Estafilocócicas/microbiología , Anticuerpos Monoclonales/uso terapéutico , Fagocitos/metabolismo , Leucocidinas/metabolismo , Leucocidinas/uso terapéutico

RESUMEN

Single-chain fragment variable (scFv) domains play an important role in antibody-based therapeutic modalities, such as bispecifics, multispecifics and chimeric antigen receptor T cells or natural killer cells. However, scFv domains exhibit lower stability and increased risk of aggregation due to transient dissociation ("breathing") and inter-molecular reassociation of the two domains (VL and VH). We designed a novel strategy, referred to as stapling, that introduces two disulfide bonds between the scFv linker and the two variable domains to minimize scFv breathing. We named the resulting molecules stapled scFv (spFv). Stapling increased thermal stability (Tm) by an average of 10°C. In multiple scFv/spFv multispecifics, the spFv molecules display significantly improved stability, minimal aggregation and superior product quality. These spFv multispecifics retain binding affinity and functionality. Our stapling design was compatible with all antibody variable regions we evaluated and may be widely applicable to stabilize scFv molecules for designing biotherapeutics with superior biophysical properties.

Asunto(s)

Anticuerpos , Región Variable de Inmunoglobulina , Región Variable de Inmunoglobulina/química , Fragmentos de Inmunoglobulinas

RESUMEN

AIMS: Lactate/albumin ratio (L/A) is a recognized prognostic index of patients with heart failure (HF) after myocardial infarction (MI). We aim to evaluate the prognostic value of L/A ratio in predicting in-hospital mortality for those patients. METHODS AND RESULTS: We enrolled qualified patients from Medical Information Mart for Intensive Care IV database for retrospective study. A receiver operating characteristic (ROC) curve of the subjects was applied to determine the predicted value and the best cut-off value of L/A on admission. Univariate/multivariate Cox regression analysis and restricted cubic splines (RCS) were performed to identify the association between hospital admission and hospital mortality. The Kaplan-Meier (KM) method was used to draw the survival curve of the two groups with different L/A levels at admission. L/A values at admission were significantly higher in the death groups than the survival groups [1.36 (1.20) vs. 0.62 (0.36), P < 0.05], and area under the ROC curve [0.780 (95% confidence interval, 0.772-0.827)] was better than other indicators, and the best the cut-off value was 0.671. Data of Cox regression analysis showed that higher L/A value supposed to be an independent risk factor for in-hospital mortality. RCS analysis showed evidence of an increasing trend and a non-linear relationship between L/A and in-hospital mortality (P value was non-linear <0.05). KM survival curves were significantly lower in the high L/A group than the low L/A group (P < 0.001), and the former group had an increased risk of in-hospital mortality compared with the latter one (log rank P < 0.001). CONCLUSIONS: Elevated L/A ratio on admission is an independent predictor of high in-hospital mortality in post-MI heart failure patients, which proved to be better than lactate, Sequential Organ Failure Assessment score and other related indicators.

Asunto(s)

Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Ácido Láctico , Estudios Retrospectivos , Infarto del Miocardio/complicaciones , Albúminas

RESUMEN

Objective: Adipose tissue is recognized as a crucial regulator of atrial fibrillation (AF). However, the effect of epicardial adipose tissue (EAT) on the pathophysiology of AF might be different from that of other adipose tissues. The purpose of this study was to explore the distribution features of different adipose tissues in AF patients and their relationships with left atrial (LA) remodeling and function. Methods: A total of 205 participants (including 112 AF and 93 non-AF patients) were recruited. Color doppler ultrasound was used to measure the thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue. Cardiac CT scan was performed to measure the mean thickness of EAT surrounding the whole heart (total-EAT) and specific regions, including left atrium (LA-EAT), left ventricle, right ventricle, interventricular groove, and atrioventricular groove. LA anatomical remodeling and function were measured by echocardiography, while electrical remodeling was evaluated by P-wave duration and dispersion using Electrocardiography (obtained after cardioversion or ablation in AF patients). Relationship between the thickness of different adipose tissues and LA remodeling and function was analyzed. Results: The thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue was similar between AF and non-AF patients, and had no or only weak association with LA remodeling and dysfunction. However, compared to non-AF participants, total-EAT thickness significantly increased in both paroxysmal and persistent AF patients (non-AF vs. paroxysmal AF vs. persistent AF: 6.31 ± 0.63 mm vs. 6.76 ± 0.79 mm vs. 7.01 ± 1.18 mm, P < 0.001), which was positively correlated with the LA size and P-wave duration and dispersion, and negatively correlated with LA ejection fraction and peak strain rate. More interestingly, EAT thickness in AF patients did not increase uniformly in different regions of the heart. Compared to EAT surrounding the other regions, LA-EAT was found to accumulate more greatly, and had a closer relationship to LA remodeling and dysfunction. Multivariate logistic regression analysis also showed that LA-EAT was significantly correlated with the presence of AF (OR = 4.781; 95% CI 2.589-8.831, P < 0.001). Conclusion: Rather than other adipose tissues, accumulation and redistribution of EAT, especially surrounding the LA, is associated with LA remodeling and dysfunction in AF patients.

RESUMEN

Background: Hypoalbuminemia is common in congestive heart failure (CHF) patients. Serum albumin is associated with the prognosis of CHF patients. Impact of albumin infusion on prognosis of patients with CHF-hypoalbuminemia overlap remains unclear. We retrospectively investigated the impact of albumin infusion on prognosis of intensive care unit (ICU) patients with CHF-hypoalbuminemia overlap. Methods: We enrolled all patients whose diagnosis included CHF [ICD-9 (international classification of diseases 9) code =428.0] at first ICU admission from the MIMIC III (Medical Information Mart for Intensive Care III) database, and excluded those with missing serum albumin values, with serum albumin >3.4 g/dL or <18 years old. According to the exposure of albumin infusion during hospitalization, patients were stratified into non-albumin and albumin groups. Propensity-score matching (PSM) was performed (1:1 ratio) to control for baseline confounding. Outcome measures were in-hospital mortality as well as length of stay in the ICU (ICU LOS) and the hospital (hospital LOS). Results: There were 3,190 eligible patients in the initial search. Patients with albumin infusion had markedly higher in-hospital mortality (36.42% vs. 21.81%, P<0.001), longer ICU LOS [median 6.93 (3.39-14.82) vs. 3.84 (1.96-8.00) days, P<0.001], and longer hospital LOS [median 17.46 (11.45-28.33) vs. 10.92 (6.81-18.00) days, P<0.001] than those without albumin infusion. The multivariate logistic regression analysis revealed that albumin infusion [odds ratio (OR), 1.509; 95% confidence interval (CI), 1.164-1.957; P=0.002] was significantly associated with increased risk of in-hospital mortality. After PSM, a cohort of 429 pairs of patients was included in the final analysis. Patients with albumin infusion had markedly higher in-hospital mortality (34.97% vs. 27.27%, P=0.015), longer ICU LOS [median 8.43 (4.33-16.28) vs. 6.43 (3.07-13.66) days, P<0.001], and longer hospital LOS [median 16.92 (11.27-28.06) vs. 13.33 (8.00-21.10) days, P<0.001] than those without albumin infusion. The multivariate logistic regression analysis revealed that albumin infusion (OR, 1.594; 95% CI, 1.143-2.223; P=0.006) was significantly associated with increased risk of in-hospital mortality. Conclusions: Albumin infusion increased in-hospital mortality, ICU LOS, and hospital LOS in ICU patients with CHF-hypoalbuminemia overlap.

RESUMEN

Background: Coronary sinus (CS) blood sampling gives an insight into the localized pathophysiology of heart diseases. However, additional specifically-designed or modified catheters were needed in most previous studies, making the convenience of clinical application unsatisfactory. This study aimed to introduce a simple method for CS blood sampling without using additional catheters during catheter ablation (CA) of arrhythmias, and to investigate its feasibility and safety. Methods: A total of 119 patients undergoing CA were prospectively enrolled, including 25 with paroxysmal supraventricular tachycardia (PSVT), 30 with premature ventricular complexes (PVC), and 64 with atrial fibrillation (AF). Cannulation and sampling of CS was performed via the femoral vein using a conventional 8F SR0TM or 8.5F SL1TM introducer sheath (St. Jude Medical) guided by a 6F steerable diagnostic catheter (St. Jude Medical). The success rate and any suspicious complications were recorded. Untargeted liquid chromatograph-mass spectrometer (LC-MS)-based metabonomics of CS samples versus peripheral venous samples were also performed. Results: CS blood samples were successfully collected from 114 patients, with an overall success rate of 95.8%. Among patients with different arrhythmias, the success rates were similar, with 96.0% in PSVT, 96.7% in PVC, and 95.3% in AF (P=0.223). Adverse events occurred in four (3.4%) patients, including two patients with occasional atrial ectopic beats without causing any discomfort, and two patients with new-onset paroxysmal AF lasting for about 2 min. No serious complications were noted. Metabonomics analysis showed that CS samples provided a number of different metabolites (93 in PVST, 217 in PVC, and 109 in AF) versus peripheral samples. Conclusions: Our method for CS blood sampling during CA is feasible and safe, and can provide useful cardiometabolic information that is significantly different from a peripheral sample.

RESUMEN

Background: Hyperhomocysteinemia is a risk factor for contrast-induced nephropathy. Folic acid can attenuate such nephropathies in rats. The protective effect of folic acid against contrast-induced nephropathy has not been studied in humans. We aimed to investigate the effect of folic acid on the incidence of contrast-induced nephropathy (CIN) after coronary catheterization in patients with hyperhomocysteinemia. Methods: This was a single-center, prospective, double-blind, randomized controlled trial (ClinicalTrials.gov, NCT02444013). In total, 412 patients (mean age: 65 ± 12 years, 268 male) with plasma homocysteine ≥15 µM, who underwent coronary arteriography (CAG) or percutaneous coronary intervention (PCI) from May 2015 to August 2018, were enrolled. Patients were randomly assigned to two groups: a treatment group (n = 203), taking 5 mg of folic acid (orally, three times/day) immediately after enrollment and for 72 h after operation, and a control group (n = 209), taking placebo. Contrast-induced nephropathy was defined as an increase in serum creatinine of >25% or 44 µM within 48 or 72 h after contrast medium administration. Results: In total, 50 (12%) patients developed CIN after 48 h after catheterization, including 16 (8%) in the treatment group and 34 (16%) in the control group (P = 0.009). Meanwhile, 53 (13%) patients developed CIN after 72 h of CAG/PCI, including 18 (9%) in the treatment group and 35 (17%) in the control group (P = 0.017). The incidence of contrast-induced nephropathy in the treatment group was lower than that in the control group (P = 0.017). Logistic regression analysis confirmed that administration of folic acid was a protective factor against contrast-induced nephropathy (RD = 0.0788, 95%CI: 0.0105-0.1469, P = 0.019). We found no serious adverse events associated with folic acid. No death or hemodialysis occurred in either group. Conclusions: Perioperative administration of folic acid attenuates the incidence of contrast-induced nephropathy after coronary catheterization in patients with hyperhomocysteinemia. Clinical Trial Registration: ClinicalTrials.gov, identifier [NCT02444013].

RESUMEN

BACKGROUND: The association between atrial fibrillation (AF) and cirrhosis is unclear. Therefore, the aim of the present study was to determine the association between AF and short-term and 4-year mortality in critically ill patients with cirrhosis using a large database. METHODS: The Medical Information Mart for Intensive Care III (MIMIC III) database was used to identify patients with cirrhosis hospitalized in an intensive care unit from 2001 to 2012. Demographic and clinical data were extracted from the database. Clinical data and demographic information were collected for each patient in our study. Kaplan-Meier analysis and multivariate Cox regression models were performed to examine the relation between atrial fibrillation and in-hospital and 4-year all-cause mortality. RESULTS: A total of 1,481 patients (mean age: 58 years, 68% male) with liver cirrhosis were included in the analysis, and the prevalence of AF was 14.18%. The inpatient all-cause mortality rate was 26.6%, and patients who died in hospital had a significantly higher rate of AF (21.57% vs. 11.50%, P<0.001). Multivariate Cox regression analysis indicated that AF was significantly associated with inpatient all-cause mortality [hazard ratio (HR): 1.52, 95% confidence interval (CI): 1.19-1.95, P<0.001], and 4-year all-cause mortality (HR: 1.55, 95% CI: 1.12-2.13, P=0.008). Kaplan-Meier survival analysis showed that patients with AF had a significantly higher inpatient and 4-year all-cause mortality. CONCLUSIONS: Critically ill patients with liver cirrhosis have a high rate of AF, and the presence of AF is an independent risk factor for inpatient and 4-year all-cause mortality.

RESUMEN

The impact of beta2-agonists (B2As) on heart failure (HF) remains controversial. This study aimed to investigate whether inhaled B2As increased in-hospital mortality in ICU patients with HF.The Multiparameter Intelligent Monitoring in Intensive Care III database was initially searched to identify adult patients (≥ 18 years old) with HF in ICU. Then, patients using or not using inhaled B2As were matched using propensity score matching on a 1:1 basis to control for baseline confounders. In-hospital mortality was compared between the two groups, and logistic regression analysis was performed to assess the association between B2As and in-hospital mortality.The initial search retrieved 2345 eligible patients with HF from the database. After propensity score matching, 705 pairs of patients were included in the final analysis. Patients using B2As had markedly higher in-hospital mortality than those not using B2As (4.68% versus 2.27%; P = 0.013). In the multivariate logistic regression analysis, B2A use (odd ratios (OR), 2.471; 95% confidence interval (CI), 1.289-4.734; P = 0.006), stroke (OR, 4.581; 95% CI, 1.621-12.948; P = 0.004), and simplified acute physiology score II (SAPS-II) scores (OR, 1.090; 95% CI, 1.064-1.116; P < 0.001) were significantly associated with increased risk of in-hospital mortality, whereas renin angiotensin system inhibitor use (OR, 0.396; 95% CI, 0.202-0.778; P = 0.007) was significantly associated with decreased risk of in-hospital mortality. Subgroup analysis further indicated that the association between B2A use and mortality was significant only in patients with HF without chronic pulmonary disease (OR, 2.427; 95% CI, 1.351-4.362; P = 0.003), but not in those with chronic pulmonary disease (OR, 2.094; 95% CI, 0.582-7.537; P = 0.258).In ICU patients with HF but without chronic pulmonary disease, the use of inhaled B2As is associated with increased in-hospital mortality.

Asunto(s)

Agonistas de Receptores Adrenérgicos beta 2/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Mortalidad Hospitalaria/tendencias , Unidades de Cuidados Intensivos/estadística & datos numéricos , Administración por Inhalación , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Anciano , Anciano de 80 o más Años , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Humanos , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Análisis de Regresión , Sistema Renina-Angiotensina/efectos de los fármacos , Estudios Retrospectivos

RESUMEN

Objective: Many tissues contained resident mesenchymal stromal/stem cells (MSCs) that facilitated tissue hemostasis and repair. However, there is no typical marker to identify the resident cardiac MSCs. We aimed to determine if CD51 could be an optimal marker of cardiac MSCs and assess their therapeutic potential for mice with acute myocardial infarction (AMI). Methods: Cardiac-derived CD51+CD31-CD45-Ter119- cells (named CD51+cMSCs) were isolated from C57BL/6 mice(7-day-old) by flow cytometry. The CD51+cMSCs were characterized by proliferation capacity, multi-differentiation potential, and expression of typical MSC-related markers. Adult C57BL/6 mice (12-week-old) were utilized for an AMI model via permanently ligating the left anterior descending coronary artery. The therapeutic efficacy of CD51+cMSCs was estimated by echocardiography and pathological staining. To determine the underlying mechanism, lentiviruses were utilized to knock down gene (stem cell factor [SCF]) expression of CD51+cMSCs. Results: In this study, CD51 was expressed in the entire layers of the cardiac wall in mice, including endocardium, epicardium, and myocardium, and its expression was decreased with age. Importantly, the CD51+cMSCs possessed potent self-renewal potential and multi-lineage differentiation capacity in vitro and also expressed typical MSC-related surface proteins. Furthermore, CD51+cMSC transplantation significantly improved cardiac function and attenuated cardiac fibrosis through pro-angiogenesis activity after myocardial infarction in mice. Moreover, SCF secreted by CD51+cMSCs played an important role in angiogenesis both in vivo and in vitro. Conclusions: Collectively, CD51 is a novel marker of cardiac resident MSCs, and CD51+cMSC therapy enhances cardiac repair at least partly through SCF-mediated angiogenesis.

RESUMEN

The application of fluoropyrimidine-based neoadjuvant chemoradiotherapy (Fu-nCRT) of locally advanced rectal cancer (LARC) has become a common therapeutic regimen. In order to improve the efficacy and enable more patients to benefit from this treatment, an accumulation of studies have been carried out on the auxiliary use of other drugs with Fu-nCRT. However, due to specific challenges and the potential opportunities that coexist in this field, a more reasonable approach to the mode of treatment remains to be explored. In this review, we have summarized the results of the studies on the combination of Fu-nCRT with cytotoxic drugs, anti-tumor angiogenesis, and anti-EGFR agents, as well as the status of the application of immune checkpoint inhibitors in the neoadjuvant therapy of LARC patients.

RESUMEN

BACKGROUND: This study sought to examine the association between the albumin-bilirubin (ALBI) score and short-term and 4-year all-cause mortality in critically ill patients with heart failure (HF), and to build a simple and effective new predictive model. METHODS: The Monitoring in Intensive Care Database III was used to identify patients with HF who had been admitted to the intensive care unit (ICU) from 2001 to 2012. Correlations between ALBI scores and other commonly used risk-scoring methods and short-term and 4-year all-cause mortality were examined using the Kaplan-Meier method and Cox proportional hazards-regression models. RESULTS: The data of 3,381 ICU patients were included in the study, of whom 53.7% were male. The patients had a mean age of 70.02±12.55 years, and a short-term mortality rate of 27.7%. The ALBI score of survivors [-1.80 (-2.09 to -1.44)] was significantly lower than that of non-survivors [-1.43 (-1.80 to -0.99)] (P<0.001), and independently predicted short-term all-cause mortality and higher 4-year mortality. The area under the receiver operating characteristic curve (AUC) of the ALBI score for short-term mortality was 0.676, and that of the Get With the Guidelines-Heart Failure (GWTG-HF) score was 0.643. The new model, which combined the ALBI and GWTG-HF (the GWTG-HF-ALBI), had an AUC of 0.713. The AUC of the ALBI score for predicting 4-year all-cause mortality was 0.596, that of the GWTG-HF score was 0.638, and that of the GWTG-HF-ALBI risk score was 0.650. CONCLUSIONS: The ALBI score is useful at predicting the mortality of patients with HF requiring ICU admission. The GWTG-HF-ALBI model is simpler to use than other models that contain subjective items, such as the Glasgow Coma Score, and can be used to predict the short-term and 4-year all-cause mortality of these patients.

Asunto(s)

Albúminas , Bilirrubina , Insuficiencia Cardíaca , Anciano , Anciano de 80 o más Años , Enfermedad Crítica , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos