Prognostic Value of Blood Urea Nitrogen for Short-Term Mortality in Patients with Infective Endocarditis.

INTRODUCTION: Blood urea nitrogen (BUN) is a metabolic product validated to be an independent risk factor in the prognosis of several diseases. However, the prognostic value of BUN in patients with infective endocarditis (IE) remains unevaluated. METHODS: A total of 1371 patients with a diagnosis of IE were included and divided into four groups according to BUN (mmol/L) at admission: < 3.5 (n = 343), 3.5-4.8 (n = 343), 4.8-6.8 (n = 341), and ≥ 6.8 (n = 344). Restricted cubic spline was used to assess the association of BUN with in-hospital mortality. Multivariate analysis was performed to identify the independent risk factors for adverse outcomes. RESULTS: The in-hospital mortality reached 7.4%, while the 6-month mortality was 9.8%. The restricted cubic spline plot exhibited an approximately linear relationship between BUN and in-hospital mortality. Receiver operating characteristics curve analysis showed that the optimal cut-off of BUN for predicting in-hospital death was 6.8 mmol/L. Kaplan-Meier analysis showed that patients with BUN > 6.8 mmol/L had a higher 6-month mortality than other groups (log rank = 97.9, P < 0.001). Multivariate analysis indicated that BUN > 6.8 mmol/L was an independent predictor indicator for both in-hospital [adjusted odds ratio (aOR) = 2.365, 95% confidence interval (CI) 1.292-4.328, P = 0.005] and 6-month mortality [adjusted hazard ratio (aHR) = 2.171, 95% CI 1.355-3.479, P = 0.001]. CONCLUSIONS: BUN is suitable for independently predicting short-term mortality in patients with IE.

LIN28A attenuates high glucose-induced retinal pigmented epithelium injury through activating SIRT1-dependent autophagy.

AIM: To evaluate the effects of LIN28A (human) on high glucose-induced retinal pigmented epithelium (RPE) cell injury and its possible mechanism. METHODS: Diabetic retinopathy model was generated following 48h of exposure to 30 mmol/L high glucose (HG) in ARPE-19 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot tested the expression of the corresponding genes and proteins. Cell viability as well as apoptosis was determined through cell counting kit-8 (CCK-8) and flow cytometry assays. Immunofluorescence assay was adopted to evaluate autophagy activity. Caspase 3 activity, oxidative stress markers, and cytokines were appraised adopting their commercial kits, respectively. Finally, ARPE-19 cells were preincubated with EX527, a Sirtuin 1 (SIRT1) inhibitor, prior to HG stimulation to validate the regulatory mechanism. RESULTS: LIN28A was downregulated in HG-challenged ARPE-19 cells. LIN28A overexpression greatly inhibited HG-induced ARPE-19 cell viability loss, apoptosis, oxidative damage as well as inflammatory response. Meanwhile, the repressed autophagy and SIRT1 in ARPE-19 cells challenged with HG were elevated after LIN28A overexpression. In addition, treatment of EX527 greatly inhibited the activated autophagy following LIN28A overexpression and partly abolished the protective role of LIN28A against HG-elicited apoptosis, oxidative damage as well as inflammation in ARPE-19 cells. CONCLUSION: LIN28A exerts a protective role against HG-elicited RPE oxidative damage, inflammation, as well as apoptosis via regulating SIRT1/autophagy.

Long-term outcomes and potential mechanisms of offspring exposed to intrauterine hyperglycemia.

Diabetes mellitus during pregnancy, which can be classified into pregestational diabetes and gestational diabetes, has become much more prevalent worldwide. Maternal diabetes fosters an intrauterine abnormal environment for fetus, which not only influences pregnancy outcomes, but also leads to fetal anomaly and development of diseases in later life, such as metabolic and cardiovascular diseases, neuropsychiatric outcomes, reproduction malformation, and immune dysfunction. The underlying mechanisms are comprehensive and ambiguous, which mainly focus on microbiota, inflammation, reactive oxygen species, cell viability, and epigenetics. This review concluded with the influence of intrauterine hyperglycemia on fetal structure development and organ function on later life and outlined potential mechanisms that underpin the development of diseases in adulthood. Maternal diabetes leaves an effect that continues generations after generations through gametes, thus more attention should be paid to the prevention and treatment of diabetes to rescue the pathological attacks of maternal diabetes from the offspring.

Optimal threshold of urinary albumin-to-creatinine ratio (UACR) for predicting long-term cardiovascular and noncardiovascular mortality.

PURPOSE: Traditional cutoff values of urinary albumin-to-creatinine ratio (UACR) for predicting mortality have recently been challenged. In this study, we investigated the optimal threshold of UACR for predicting long-term cardiovascular and non-cardiovascular mortality in the general population. METHODS: Data for 25,302 adults were extracted from the National Health and Nutrition Examination Survey (2005-2014). Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive value of UACR for cardiovascular and non-cardiovascular mortality. A Cox regression model was established to examine the association between UACR and cardiovascular and non-cardiovascular mortality. X-tile was used to estimate the optimal cutoff of UACR. RESULTS: The UACR had acceptable predictive value for both cardiovascular (AUC (95% CI) for 1-year, 3-year and 5-year mortality, respectively: 0.769 (0.711-0.828), 0.764 (0.722-0.805) and 0.763 (0.730-0.795)) and non-cardiovascular (AUC (95% CI) for 1-year, 3-year and 5-year mortality, respectively: 0.772 (0.681-0.764), 0.708 (0.686-0.731) and 0.708 (0.690-0.725)) mortality. The optimal cutoff values were 16 and 30 mg/g for predicting long-term cardiovascular and non-cardiovascular mortality, respectively. Both cutoffs of UACR had acceptable specificity (0.785-0.891) in predicting long-term mortality, while the new proposed cutoff (16 mg/g) had higher sensitivity. The adjusted hazard ratios of cardiovascular and non-cardiovascular mortality for the high-risk group were 2.50 (95% CI 1.96-3.18, P < 0.001) and 1.92 (95% CI 1.70-2.17, P < 0.001), respectively. CONCLUSIONS: Compared to the traditional cutoff value (30 mg/g), a UACR cutoff of 16 mg/g may be more sensitive for identifying patients at high risk for cardiovascular mortality in the general population.

The effect of medication on serum anti-müllerian hormone (AMH) levels in women of reproductive age: a meta-analysis.

OBJECTIVE: The study aims to address whether serum anti-müllerian hormone (AMH) levels fluctuate in the short term after medication application, including oral contraceptives (OCs), metformin (MET), Gonadotropin-releasing hormone agonist (GnRH-a), dehydroepiandrosterone (DHEA), vitamin D (VD), clomiphene citrate (CC), and letrozole (LET). METHODS: Published literature from PubMed, Embase, and Cochrane central was retrieved up until 19 September 2021. A total of 51 self-control studies with an average Newcastle-Ottawa quality assessment scale (NOS) score of 6.90 were analyzed. The extracted data were entered into Stata software, and the weighted mean difference/standardized mean difference (WMD/SMD) and 95% confidence interval (CI) were used for data analysis. RESULTS: After OCs treatment the AMH level showed a significant decline in women with normal ovarian function, which was significant within 3 months (WMD = -1.43, 95% CI: -2.05 to -0.80, P < 0.00001). After MET treatment, the serum AMH decreased in polycystic ovary syndrome (PCOS) patients (WMD = -1.79, 95% CI: -2.32 to -1.26, P < 0.00001), in both obese and non-obese patients. GnRH-a treatment in endometriosis patients led to dynamic changes in the serum AMH levels, that is, ascent at 1 month (P = 0.05), and descent at 3 months (P = 0.02). After DHEA treatment the serum AMH increased in diminished ovarian reserve (DOR) / poor ovarian response (POR) patients (WMD = 0.18, 95% CI: 0.09 to 0.27, P < 0.0001). After VD treatment the serum AMH increased, and it was obvious in non-PCOS patients (WMD = 0.78, 95% CI: 0.34 to 1.21, P = 0.0004). After CC treatment the serum AMH decreased significantly in PCOS patients, specifically in non-obese patients (WMD = -1.24, 95% CI: -1.87 to -0.61, P = 0.0001). CONCLUSIONS: Serum AMH levels may be affected in the short term after drug application. Specifically, OC, MET and CC lead to decreased AMH level, DHEA and VD lead to increased AMH level, and GnRH-a leads to dynamic variation, which is correlated with PCOS, obesity, age, and duration of medication. The impacts of these medications should be taken into consideration when AMH is used as a marker of ovarian reserve.

Albumin-Bilirubin Score to Predict Outcomes in Patients with Idiopathic Dilated Cardiomyopathy. / Escore Albumina-Bilirrubina para Predizer Desfechos em Pacientes com Cardiomiopatia Dilatada Idiopática.

BACKGROUND: Liver dysfunction is a postulated variable for poor prognosis in dilated cardiomyopathy (DCM). OBJECTIVE: This study aimed to investigate the prognostic value of the albumin-bilirubin (ALBI) score, a relatively new model for evaluating liver function, in patients with idiopathic DCM. METHODS: A total of 1025 patients with idiopathic DCM were retrospectively included and divided into three groups based on ALBI scores: grade 1 (≤ -2.60, n = 113), grade 2 (-2.60 to -1.39, n = 835), and grade 3 (> -1.39, n = 77). The association of ALBI score with in-hospital major adverse clinical events (MACEs) and long-term mortality was analyzed. P-value less than 0.05 was considered statistically significant. RESULTS: The in-hospital MACEs rate was significantly higher in the grade 3 patients (2.7% versus 7.1% versus 24.7%, p < 0.001). Multivariate analysis showed that ALBI score was an independent predictor for in-hospital MACEs (adjusted odds ratio = 2.80, 95%CI: 1.63 - 4.80, p < 0.001). After a median 27-month follow-up, 146 (14.2%) patients died. The Kaplan-Meier curve indicated that the cumulative rate of long-term survival was significantly lower in patients with higher ALBI grade (log-rank = 45.50, p < 0.001). ALBI score was independently associated with long-term mortality (adjusted hazard ratio = 2.84, 95%CI: 1.95 - 4.13, p < 0.001). CONCLUSION: ALBI score as a simple risk model could be considered a risk-stratifying tool for patients with idiopathic DCM.

FUNDAMENTO: A disfunção hepática é uma variável postulada de prognóstico desfavorável na cardiomiopatia dilatada (CMD). OBJETIVO: Este estudo teve como objetivo investigar o valor prognóstico do escore albumina-bilirrubina (ALBI), um modelo relativamente novo para a avaliação da função hepática, em pacientes com CMD idiopática. MÉTODOS: Um total de 1.025 pacientes com CMD idiopática foram incluídos retrospectivamente e divididos em três grupos com base nos escores de ALBI: grau 1 (≤ −2,60, n = 113), grau 2 (−2,60 a −1,39, n = 835) e grau 3 (> −1,39, n = 77). Foi analisada a associação do escore ALBI com eventos clínicos adversos maiores (ECAM) intra-hospitalares e mortalidade a longo prazo. Valor de p inferior a 0,05 foi considerado estatisticamente significativo. RESULTADOS: A taxa de ECAM intra-hospitalares foi significativamente maior nos pacientes com grau 3 (2,7% versus 7,1% versus 24,7%, p < 0,001). A análise multivariada mostrou que o escore ALBI foi um preditor independente para ECAM intra-hospitalares (odds ratio ajustada = 2,80, IC 95%: 1,63 ­ 4,80, p < 0,001). Após seguimento mediano de 27 meses, 146 (14,2%) pacientes morreram. A curva de Kaplan-Meier indicou que a taxa cumulativa de sobrevida a longo prazo foi significativamente menor em pacientes com grau mais alto de ALBI (log-rank = 45,50, p < 0,001). O escore ALBI foi independentemente associado à mortalidade a longo prazo (hazard ratio ajustada = 2,84, IC 95%: 1,95 ­ 4,13, p < 0,001). CONCLUSÃO: O escore ALBI, como modelo de risco simples, pode ser considerado uma ferramenta de estratificação de risco para pacientes com CMD idiopática.

Estimated glomerular filtration rate derived from different formulas and prognosis in acute coronary syndrome: Findings from the improving care for cardiovascular disease in China-acute coronary syndrome project.

BACKGROUND: The optimal formula for the estimation of glomerular filtration rate (GFR) in patients with acute coronary syndrome (ACS) in terms of predicting in-hospital mortality and adverse events remains unclear. METHODS: A nationwide registry study, Improving CCC (Care for Cardiovascular Disease in China) ACS project, was launched in 2014 as a collaborative study of the American Heart Association and Chinese Society of Cardiology. The Cockcroft-Gault, modification of diet in renal disease (MDRD) formula for Chinese (C-MDRD), Mayo, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were used to calculate estimated GFR in 61,545 ACS patients (38,734 with ST-segment elevation myocardial infarction [STEMI] and 22,811 with non-ST-segment-elevation ACS [NSTE-ACS]). RESULTS: Prevalence of moderate to severe renal dysfunction was inconsistent among four formulas, ranging from 11.6% to 22.4% in NSTE-ACS and from 8.3% to 16.8% in STEMI, respectively. The in-hospital mortality rate in patients with ACS was inversely associated with estimated GFR. In STEMI, the Mayo-derived eGFR exhibited the highest predictive power for in-hospital death compared with the Cockcroft-Gault-derived eGFR (area under the curve [AUC]: 0.782 vs. 0.768, p=0.004), C-MDRD-derived eGFR (AUC: 0.782 vs. 0.740, p<0.001) and CKD-EPI-derived eGFR (AUC: 0.782 vs. 0.767, p<0.001). In NSTE-ACS, the Mayo-derived eGFR exhibited a similar predictive value with the Cockcroft-Gault (AUC: 0.781 vs. 0.787, p>0.05) and CKD-EPI-derived eGFR (AUC: 0.781 vs. 0.784, p>0.05). CONCLUSIONS: The Mayo formula was superior to Cockcroft-Gault, C-MDRD, and CKD-EPI formulas for predicting in-hospital mortality in ACS patients, especially for STEMI. The Mayo-derived eGFR may serve as a risk-stratification tool for in-hospital adverse events in ACS patients. CLINICAL TRIAL REGISTRATION: URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT02306616.

Corrigendum: Prevalence and Prognostic Significance of Malnutrition in Hypertensive Patients in a Community Setting.

[This corrects the article DOI: 10.3389/fnut.2022.822376.].

Endovascular embolization of spontaneous massive hemorrhage of a facial plexiform neurofibroma: case report and literature review.

BACKGROUND: As a subtype of neurofibromatosis, the plexiform neurofibroma is a benign, autosomally inherited disorder and predisposed to tumour formation. However, life-threatening haemorrhage into facial plexiform neurofibroma is extremely rare. CASE INFORMATION: In the current study, we showed a facial plexiform neurofibroma case with massive haemorrhage in the cranio-maxillofacial region. An emergent selective angiography of the external carotid artery was performed to identify the offending artery, which was then selectively occluded by the combination of detachable coils and Onyx-34. Thus, the minimally invasive drainage surgery was successfully performed to evacuate the haematoma. CONCLUSION: We believe the endovascular embolization achieved its purpose by providing an initial salvage strategy for stopping active haemorrhage in plexiform neurofibroma, allowing surgeons to perform open surgery with lower complications rate.

Escore Albumina-Bilirrubina para Predizer Desfechos em Pacientes com Cardiomiopatia Dilatada Idiopática / Albumin-Bilirubin Score to Predict Outcomes in Patients with Idiopathic Dilated Cardiomyopathy

Resumo Fundamento: A disfunção hepática é uma variável postulada de prognóstico desfavorável na cardiomiopatia dilatada (CMD). Objetivo: Este estudo teve como objetivo investigar o valor prognóstico do escore albumina-bilirrubina (ALBI), um modelo relativamente novo para a avaliação da função hepática, em pacientes com CMD idiopática. Métodos: Um total de 1.025 pacientes com CMD idiopática foram incluídos retrospectivamente e divididos em três grupos com base nos escores de ALBI: grau 1 (≤ −2,60, n = 113), grau 2 (−2,60 a −1,39, n = 835) e grau 3 (> −1,39, n = 77). Foi analisada a associação do escore ALBI com eventos clínicos adversos maiores (ECAM) intra-hospitalares e mortalidade a longo prazo. Valor de p inferior a 0,05 foi considerado estatisticamente significativo. Resultados: A taxa de ECAM intra-hospitalares foi significativamente maior nos pacientes com grau 3 (2,7% versus 7,1% versus 24,7%, p < 0,001). A análise multivariada mostrou que o escore ALBI foi um preditor independente para ECAM intra-hospitalares (odds ratio ajustada = 2,80, IC 95%: 1,63 - 4,80, p < 0,001). Após seguimento mediano de 27 meses, 146 (14,2%) pacientes morreram. A curva de Kaplan-Meier indicou que a taxa cumulativa de sobrevida a longo prazo foi significativamente menor em pacientes com grau mais alto de ALBI (log-rank = 45,50, p < 0,001). O escore ALBI foi independentemente associado à mortalidade a longo prazo (hazard ratio ajustada = 2,84, IC 95%: 1,95 - 4,13, p < 0,001). Conclusão: O escore ALBI, como modelo de risco simples, pode ser considerado uma ferramenta de estratificação de risco para pacientes com CMD idiopática.

Abstract Background: Liver dysfunction is a postulated variable for poor prognosis in dilated cardiomyopathy (DCM). Objective: This study aimed to investigate the prognostic value of the albumin-bilirubin (ALBI) score, a relatively new model for evaluating liver function, in patients with idiopathic DCM. Methods: A total of 1025 patients with idiopathic DCM were retrospectively included and divided into three groups based on ALBI scores: grade 1 (≤ −2.60, n = 113), grade 2 (−2.60 to −1.39, n = 835), and grade 3 (> −1.39, n = 77). The association of ALBI score with in-hospital major adverse clinical events (MACEs) and long-term mortality was analyzed. P-value less than 0.05 was considered statistically significant. Results: The in-hospital MACEs rate was significantly higher in the grade 3 patients (2.7% versus 7.1% versus 24.7%, p < 0.001). Multivariate analysis showed that ALBI score was an independent predictor for in-hospital MACEs (adjusted odds ratio = 2.80, 95%CI: 1.63 - 4.80, p < 0.001). After a median 27-month follow-up, 146 (14.2%) patients died. The Kaplan-Meier curve indicated that the cumulative rate of long-term survival was significantly lower in patients with higher ALBI grade (log-rank = 45.50, p < 0.001). ALBI score was independently associated with long-term mortality (adjusted hazard ratio = 2.84, 95%CI: 1.95 - 4.13, p < 0.001). Conclusion: ALBI score as a simple risk model could be considered a risk-stratifying tool for patients with idiopathic DCM.

A Risk Stratification Scheme for In-Hospital Cardiogenic Shock in Patients With Acute Myocardial Infarction.

Objective: Cardiogenic shock (CS) is the leading cause of death in patients with acute myocardial infarction (AMI) despite advances in care. This study aims to derive and validate a risk score for in-hospital development of CS in patients with AMI. Methods: In this study, we used the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) registry of 76,807 patients for model development and internal validation. These patients came from 158 tertiary hospitals and 82 secondary hospitals between 2014 and 2019, presenting AMI without CS upon admission. The eligible patients with AMI were randomly assigned to derivation (n = 53,790) and internal validation (n = 23,017) cohorts. Another cohort of 2,205 patients with AMI between 2014 and 2016 was used for external validation. Based on the identified predictors for in-hospital CS, a new point-based CS risk scheme, referred to as the CCC-ACS CS score, was developed and validated. Results: A total of 866 (1.1%) and 39 (1.8%) patients subsequently developed in-hospital CS in the CCC-ACS project and external validation cohort, respectively. The CCC-ACS CS score consists of seven variables, including age, acute heart failure upon admission, systolic blood pressure upon admission, heart rate, initial serum creatine kinase-MB level, estimated glomerular filtration rate, and mechanical complications. The area under the curve for in-hospital development of CS was 0.73, 0.71, and 0.85 in the derivation, internal validation and external validation cohorts, respectively. Conclusion: This newly developed CCC-ACS CS score can quantify the risk of in-hospital CS for patients with AMI, which may help in clinical decision making. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02306616.

Prevalence and Prognostic Significance of Malnutrition in Hypertensive Patients in a Community Setting.

Background: Malnutrition is a significantly poor prognostic factor for a variety of cardiovascular diseases. However, its prevalence and prognostic value in hypertensive patients is still unclear. The present study sought to determine the prevalence and prognostic value of malnutrition in hypertensive patients in a community setting. Methods: We included 9,949 hypertensive patients from the National Health and Nutrition Examination Survey (NHANES) (2005-2014). The Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Naples Prognostic Score (NPS) were applied to assess the nutritional status of participants. A Cox regression model was established to examine the association between malnutrition and cardiovascular and all-cause mortality. Results: In all, 19.9, 3.9, and 82.9% hypertensive patients were considered to have malnutrition as evaluated by the CONUT, NRI, and NPS, respectively. Malnutrition assessed by CONUT and NRI was independently associated with cardiovascular mortality (HR [95% CI]) for mild and moderate-to-severe degree of malnutrition, respectively: 1.41 (1.04-1.91) and 5.79 (2.34-14.29) for CONUT; 2.60 (1.34-5.07) and 3.30 (1.66-6.56) for NRI (all P < 0.05), and for all-cause mortality (HR [95% CI]) for mild and moderate-to-severe degree of malnutrition, respectively: 1.48 (1.30-1.70) and 4.87 (3.40-6.98) for CONUT; 1.72 (1.24-2.39) and 2.60 (1.96-3.44) for NRI (all P < 0.01). Naples Prognostic Score could only independently predict all-cause mortality. Conclusions: Malnutrition was common among hypertensive patients and was closely associated with both long-term cardiovascular and all-cause mortality.

The effect of preoperative statin treatment on acute kidney injury in elderly patients undergoing valve replacement surgery.

PURPOSES: The effects of preoperative statin treatment on acute kidney injury (AKI) remain controversial, and current clinical evidence regarding statin use in the elderly undergoing valve replacement surgery (VRS) is insufficient. The present study aimed to investigate the association between preoperative statin treatment and AKI after VRS in the elderly. METHODS: Three thousand seven hundred ninety-one elderly patients (≥ 60 years) undergoing VRS were included in this study and divided into 2 groups, according to the receipt of statin treatment before the operation: statin users (n = 894) and non-users (n = 2897). We determined the associations between statin use, AKI, and other adverse events using a multivariate model and propensity score-matched analysis. RESULTS: After propensity score-matched analysis, there was no difference between statin users and non-users in regard to postoperative AKI (72.5% vs. 72.4%, p = 0.954), in-hospital death (5.7% vs. 5.1%, p = 0.650) and 1-year mortality (log-rank = 0, p = 0.986). The multivariate analysis showed that statin use was not an independent risk factor for postoperative AKI (OR = 0.97, 95% CI: 0.90-1.17, p = 0.733), in-hospital mortality (OR = 1.12, 95% CI: 0.75-1.68, p = 0.568), or 1-year mortality (HR = 0.95, 95% CI: 0.70-1.28, p = 0.715). CONCLUSION: Preoperative statin treatment did not significantly affect the risk of AKI among elderly patients undergoing VRS.

Glycemic control and neonatal outcomes in women with gestational diabetes mellitus treated using glyburide, metformin, or insulin: a pairwise and network meta-analysis.

AIMS: We aimed to assess the comparative efficiency and safety of the use of glyburide, metformin, and insulin in gestational diabetes mellitus (GDM). METHODS: We searched for randomized controlled trials that compared glyburide, metformin, and insulin in GDM. Data regarding glycemic control and neonatal safety were collected and analyzed in pairwise and network meta-analyses. RESULTS: A total of 4533 individuals from 23 trials were included. Compared with glyburide, metformin reduced 2-h postprandial blood glucose (2HPG) to a greater extent (standard mean difference (SMD) 0.18; 95% credible interval (CI) 0.01, 0.34). There were significantly lower prevalence of neonatal hypoglycemia (risk difference (RD) - 0.07; 95%CI - 0.11, - 0.02) and preeclampsia (RD - 0.03; 95%CI - 0.06, 0) in the metformin group than in the insulin group. The metformin group had significantly lower birth weight (SMD - 0.17; 95%CI - 0.25, - 0.08) and maternal weight gain (SMD - 0.61; 95%CI - 0.86,- 0.35) compared with the insulin group. Network meta-analysis suggested that metformin had the highest probability of successfully controlling glycemia and preventing neonatal complications. CONCLUSIONS: The present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications.

Association of Parenteral Anticoagulation Therapy With Outcomes in Non-ST-Segment Elevation Acute Coronary Syndrome Patients Without Invasive Therapy: Findings from the Improving Care for Cardiovascular Disease in China (CCC) project.

Our previous study showed that parenteral anticoagulation therapy (PACT) in the context of aggressive antiplatelet therapy failed to improve clinical outcomes in patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, the role of PACT in patients managed medically remains unknown. This observational cohort study enrolled patients with NSTE-ACS receiving medical therapy from November 2014 to June 2017 in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. Eligible patients were included in the PACT group and non-PACT group. The primary outcomes were in-hospital all-cause mortality and major bleeding. The secondary outcome included minor bleeding. Among 23,726 patients, 8,845 eligible patients who received medical therapy were enrolled. After adjusting the potential confounders, PACT was not associated with a lower risk of in-hospital all-cause mortality (adjusted odds ratio (OR), 1.25; 95% confidence interval (CI), 0.92-1.71; P = 0.151). Additionally, PACT did not increase the incidence of major bleeding or minor bleeding (major bleeding: adjusted OR, 1.04; 95% CI, 0.80-1.35; P = 0.763; minor bleeding: adjusted OR, 1.27; 95% CI, 0.91-1.75; P = 0.156). The propensity score analysis confirmed the primary analyses. In patients with NSTE-ACS receiving antiplatelet therapy, PACT was not associated with a lower risk of in-hospital all-cause mortality or a higher bleeding risk in patients with NSTE-ACS receiving non-invasive therapies and concurrent antiplatelet strategies. Randomized clinical trials are warranted to reevaluate the safety and efficacy of PACT in all patients with NSTE-ACS who receive noninvasive therapies and current antithrombotic strategies.

Shock Index-C: An Updated and Simple Risk-Stratifying Tool in ST-Segment Elevation Myocardial Infarction.

Background: Shock index (heart rate/systolic blood pressure, SI) is a simple scale with prognostic value in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The present study introduces an updated version of SI that includes renal function. Methods: A total of 1,851 consecutive patients with STEMI undergoing PCI were retrospectively included at Cardiac Care Unit in Guangdong Provincial People's Hospital and divided into two groups according to their admission time: derivation database (from January 2010 to December 2013, n = 1,145) and validation database (from January 2014 to April 2016, n = 706). Shock Index-C (SIC) was calculated as (SI × 100)-estimated CCr. Calibration was evaluated using the Hosmer-Lemeshow statistic. The predictive power of SIC was evaluated using receiver operating characteristic (ROC) curve analysis. Results: The predictive value and calibration of SIC for in-hospital death was excellent in derivation [area under the curve (AUC) = 0.877, p < 0.001; Hosmer-Lemeshow chi-square = 3.95, p = 0.861] and validation cohort (AUC = 0.868, p < 0.001; Hosmer-Lemeshow chi-square = 5.01, p = 0.756). SIC exhibited better predictive power for in-hospital events than SI (AUC: 0.874 vs. 0.759 for death; 0.837 vs. 0.651 for major adverse clinical events [MACEs]; 0.707 vs. 0.577 for contrast-induced acute kidney injury [CI-AKI]; and 0.732 vs. 0.590 for bleeding, all p < 0.001). Cumulative 1-year mortality was significantly higher in the upper SIC tertile (log-rank = 131.89, p < 0.001). Conclusion: SIC was an effective predictor of poor prognosis and may have potential as a novel and simple risk stratification tool for patients with STEMI undergoing PCI.

Sex Steroids and Osteoarthritis: A Mendelian Randomization Study.

Objective: Sex steroids are thought to contribute to the pathogenesis of osteoarthritis (OA). This study investigated the causal role of sex steroids in site- and sex-specific OA and risk of joint replacement surgery using the Mendelian randomization (MR) method. Methods: Instrumental variables for estradiol, dehydroepiandrosterone sulfate, testosterone (T), and dihydrotestosterone (DHT) were selected. We used the inverse variance weighting (IVW) approach as the main MR method to estimate causal effects based on the summary-level data for OA and joint replacement surgery from genome-wide association studies (GWAS). Results: A positive causal association was observed between serum T level and risks of hip OA (odds ratio [OR]=1.558, 95% confidence interval [CI]: 1.193-2.034; P=0.001) and hip replacement (OR=1.013, 95% CI: 1.008-1.018; P=2.15×10-8). Serum DHT level was also positively associated with the risk of hip replacement (OR=1.011, 95% CI: 1.006-1.015; P=4.03×10-7) and had potential causality with hip OA (OR=1.398, 95% CI: 1.054-1.855; P=0.020). Conclusions: Serum T and DHT levels may play causal roles in the development of hip OA and contribute to the risk of hip replacement, although the underlying mechanisms require further investigation.

Prognostic value of D-dimer for adverse outcomes in patients with infective endocarditis: an observational study.

BACKGROUND: Increased D-dimer levels have been shown to correlate with adverse outcomes in various clinical conditions. However, few studies with a large sample size have been performed thus far to evaluate the prognostic value of D-dimer in patients with infective endocarditis (IE). METHODS: 613 patients with IE were included in the study and categorized into two groups according to the cut-off of D-dimer determined by receiver operating characteristic (ROC) curve analysis for in-hospital death: > 3.5 mg/L (n = 89) and ≤ 3.5 mg/L (n = 524). Multivariable regression analysis was used to determine the association of D-dimer with in-hospital adverse events and six-month death. RESULTS: In-hospital death (22.5% vs. 7.3%), embolism (33.7% vs 18.2%), and stroke (29.2% vs 15.8%) were significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L. Multivariable analysis showed that D-dimer was an independent risk factor for in-hospital adverse events (odds ratio = 1.11, 95% CI 1.03-1.19, P = 0.005). In addition, the Kaplan-Meier curve showed that the cumulative 6-month mortality was significantly higher in patients with D-dimer > 3.5 mg/L than in those with D-dimer ≤ 3.5 mg/L (log-rank test = 39.19, P < 0.0001). Multivariable Cox regression analysis showed that D-dimer remained a significant predictor for six-month death (HR 1.11, 95% CI 1.05-1.18, P < 0.001). CONCLUSIONS: D-dimer is a reliable prognostic biomarker that independently associated with in-hospital adverse events and six-month mortality in patients with IE.

Analysis of risk factors for early stent thrombosis in the Chinese population: A multicenter restrospective study.

BACKGROUND: The predictive scoring systems for early stent thrombosis (EST) remains blank in China. The study aims to evaluate the risk factors and conduct a prediction model of EST in the Chinese population. METHODS: EST was defined as thrombosis that occurs within the first 30 days after primary percutaneous coronary intervention (PCI). Patients from ten Chinese hospitals diagnosed as stent thrombosis (ST) from January 2010 to December 2016 were retrospectively included as the study group. A control group (1 case:2 controls) was created by including patients without ST, major adverse cardiovascular events, or cerebrovascular events during follow-up. The present study evaluated 426 patients with single-vessel lesions and ultimately included 40 patients with EST and 80 control patients, who were included to identify factors that predicted EST and to develop a prediction scoring system. The other 171 patients without integrated 1:2 pair were used for external validation. RESULTS: EST was independently associated with a low hemoglobin concentration (adjusted odds ratio [OR] 0.946, 95% confidence interval [95% CI] 0.901-0.993, P=0.026), a high pre-PCI Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score (OR 1.166, 95% CI 1.049-1.297, P=0.004), and a DAPT (DAPT) duration of <30 days (OR 28.033, 95% CI 5.302-272.834, P<0.001). The simple EST prediction score provided an area under the curve (AUC) of 0.854 (95% CI 0.777-0.932, P<0.001) with 70.0% sensitivity and 90.0% specificity, and 0.742 (95% CI 0.649-0.835, P<0.001) with 54.5% sensitivity and 81.0% specificity for external validation dataset. CONCLUSIONS: EST may be independently associated with DAPT discontinuation within 30 days, a low hemoglobin concentration, and a high SYNTAX score. The scoring system also has a good ability to predict the risk of EST and may be useful in the clinical setting.

Melatonin alleviates lipopolysaccharide-induced myocardial injury by inhibiting inflammation and pyroptosis in cardiomyocytes.

BACKGROUND: Melatonin (MT) has been shown to protect against various cardiovascular diseases. However, the effect of MT on lipopolysaccharide (LPS)-induced myocardial injury is poorly understood. This study aims to evaluate the effects of MT on LPS-induced myocardial injury in vitro. METHODS: H9C2 cells were divided into a control group, MT group, LPS group, and MT + LPS group. The control group was treated with sterile saline solution, the LPS group received 8 µg/mL LPS for 24 h, MT + LPS cells were pretreated with 200 µmol/L MT for 2 h then with 8 µg/mL LPS for 24 h, and the MT group received only 200 µmol/L MT for 2 h. The CCK-8 assay and lactate dehydrogenase (LDH) activity assay were used to analyze cell viability and LDH release, respectively. Intracellular reactive oxygen species (ROS) and the rate of pyroptosis were measured using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) and propidium iodide (PI) staining, respectively. The cell supernatants were used to measure the levels of inflammatory cytokines, including IL-6, TNF-α, and IL-1ß by enzyme-linked immunosorbent assay (ELISA). The protein levels of iNOS, COX-2, NF-κB, p-NF-κB, NLRP3, caspase-1, and GSDMD were detected by western blot. RESULTS: MT pretreatment significantly improved LPS-induced myocardial injury by inhibiting inflammation and pyroptosis in H9C2 cells. Moreover, MT inhibited the activation of the NF-κB pathway, and reduced the expression of inflammation-related proteins (iNOS and COX-2), and pyroptosis-related proteins (NLRP3, caspase-1, and GSDMD). CONCLUSIONS: Our data suggests that MT can alleviate LPS-induced myocardial injury, providing novel insights into the treatment of sepsis-induced myocardial dysfunction.