Efficacy and safety of sacubitril/valsartan in the treatment of middle-aged and elderly patients with hypertension: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: With the increase of hypertensive patients worldwide, the need for better antihypertensive drugs to achieve blood pressure standards and reduce complications is of great clinical significance. As an angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan has been widely used in the treatment of heart failure, but its efficacy and safety in the treatment of middle-aged and elderly hypertensive patients are still controversial. Therefore, we performed a meta-analysis to compare the efficacy and safety of sacubitril/valsartan and other antihypertensive drugs in the treatment of middle-aged and elderly patients with hypertension. METHODS: The databases of PubMed, Embase, and Web of Science were systematically searched from their establishment to February 2022 to collect the randomized controlled trials (RCTs) of sacubitril/valsartan and other antihypertensive drugs in the treatment of middle-aged and elderly hypertensive patients. The Cochrane Collaboration's tool was used to assess risk of bias for included studies, and the meta-analysis was performed by using RevMan 5.3. RESULTS: In all, 7 studies which met the criteria were included, with a total sample size of 3,323 patients, including 1,899 patients treated with sacubitril/valsartan, and 1,424 patients treated with angiotensin II receptor blockers (ARBs). The meta-analysis showed that compared with other antihypertensive drugs, sacubitril/valsartan can significantly reduce mean reductions in sitting systolic blood pressure [mean difference (MD) =-4.70, 95% confidence interval (CI): -5.79 to -3.61, P<0.001], mean reductions in sitting diastolic blood pressure (MD =-2.29, 95% CI: -2.53 to -2.04, P<0.001), 24-hour mean reductions in ambulatory systolic blood pressure (MD =-3.36, 95% CI: -4.08 to -2.64, P<0.001), and 24-hour mean reductions in ambulatory diastolic blood pressure (MD =-1.49, 95% CI: -1.99 to -0.99, P<0.001), while there was no significant difference in the incidence of adverse events [odds ratio (OR) =1.14, 95% CI: 1.00 to 1.31, P=0.06], serious adverse events (OR =1.06, 95% CI: 0.64 to 1.76, P=0.81), and discontinuations due to adverse events (OR =0.86, 95% CI: 0.51 to 1.46, P=0.58). DISCUSSION: Compared with other antihypertensive drugs, sacubitril/valsartan may be more effective in lowering blood pressure, and its safety may be comparable to that of ARBs. However, these results have to be confirmed by future RCTs with larger sample sizes and higher quality, and the long-term benefits of sacubitril/valsartan require further observation.

Key Regulatory Differentially Expressed Genes in the Blood of Atrial Septal Defect Children Treated With Occlusion Devices.

Atrial septal defects (ASDs) are the most common types of cardiac septal defects in congenital heart defects. In addition to traditional therapy, interventional closure has become the main treatment method. However, the molecular events and mechanisms underlying the repair progress by occlusion device remain unknown. In this study, we aimed to characterize differentially expressed genes (DEGs) in the blood of patients treated with occlusion devices (metal or poly-L-lactic acid devices) using RNA-sequencing, and further validated them by qRT-PCR analysis to finally determine the expression of key mediating genes after closure of ASD treatment. The result showed that total 1,045 genes and 1,523 genes were expressed differently with significance in metal and poly-L-lactic acid devices treatment, respectively. The 115 overlap genes from the different sub-analyses are illustrated. The similarities and differences in gene expression reflect that the body response process involved after interventional therapy for ASDs has both different parts that do not overlap and the same part that crosses. The same portion of body response regulatory genes are key regulatory genes expressed in the blood of patients with ASDs treated with closure devices. The gene ontology enrichment analysis showed that biological processes affected in metal device therapy are immune response with CXCR4 genes and poly-L-lactic acid device treatment, and the key pathways are nuclear-transcribed mRNA catabolic process and proteins targeting endoplasmic reticulum process with ribosomal proteins (such as RPS26). We confirmed that CXCR4, TOB1, and DDIT4 gene expression are significantly downregulated toward the pre-therapy level after the post-treatment in both therapy groups by qRT-PCR. Our study suggests that the potential role of CXCR4, DDIT4, and TOB1 may be key regulatory genes in the process of endothelialization in the repair progress of ASDs, providing molecular insights into this progress for future studies.

Genetic syndromes screening by facial recognition technology: VGG-16 screening model construction and evaluation.

BACKGROUND: Many genetic syndromes (GSs) have distinct facial dysmorphism, and facial gestalts can be used as a diagnostic tool for recognizing a syndrome. Facial recognition technology has advanced in recent years, and the screening of GSs by facial recognition technology has become feasible. This study constructed an automatic facial recognition model for the identification of children with GSs. RESULTS: A total of 456 frontal facial photos were collected from 228 children with GSs and 228 healthy children in Guangdong Provincial People's Hospital from Jun 2016 to Jan 2021. Only one frontal facial image was selected for each participant. The VGG-16 network (named after its proposal lab, Visual Geometry Group from Oxford University) was pretrained by transfer learning methods, and a facial recognition model based on the VGG-16 architecture was constructed. The performance of the VGG-16 model was evaluated by five-fold cross-validation. Comparison of VGG-16 model to five physicians were also performed. The VGG-16 model achieved the highest accuracy of 0.8860 ± 0.0211, specificity of 0.9124 ± 0.0308, recall of 0.8597 ± 0.0190, F1-score of 0.8829 ± 0.0215 and an area under the receiver operating characteristic curve of 0.9443 ± 0.0276 (95% confidence interval: 0.9210-0.9620) for GS screening, which was significantly higher than that achieved by human experts. CONCLUSIONS: This study highlighted the feasibility of facial recognition technology for GSs identification. The VGG-16 recognition model can play a prominent role in GSs screening in clinical practice.

Novel and traditional anthropometric indices for identifying arterial stiffness in overweight and obese adults.

BACKGROUND: Obesity and arterial stiffness are both independently associated with cardiovascular risk. New anthropometric indices can better reflect abdominal obesity than traditional anthropometric indices. Thus, we hypothesized that compared with conventional parameters, these newly developed anthropometric parameters were more accurate to identify arterial stiffness among overweight and obesity population. METHODS: Cross-sectional data on socio-demographic, lifestyle, clinical characteristics and biochemical measurements were collected for 1442 Chinese obese and overweight adults. Six anthropometric indices including a body shape index (ABSI), body mass index (BMI), ABSI combined with BMI, body roundness index (BRI), waist circumference and waist-to-hip ratio were calculated. Carotid-femoral pulse wave velocity (cf-PWV) was detected in all subjects. Meanwhile, visceral fat area (VFA) was quantificationally measured by CT. Partial Spearman correlation coefficients were used to clarify the association between anthropometric measures with cf-PWV. Logistic regression analyses were used to identify to the association between anthropometric measures and arterial stiffness. RESULTS: After adjusting for covariates, BRI had the strongest correlation with cf-PWV and VFA in all anthropometric indices. Multivariate regression analysis showed VFA (ß = 0.322, p < 0.001) and BRI (ß = 0.307, p < 0.001) remained independently associated with cf-PWV. BRI had a highest odds ratios in all anthropometric indices (OR = 1.543, p < 0.001). ABSI only displayed a weak correlation with arterial stiffness. Meanwhile, BRI had the highest area under curve for abnormal cf-PWV, and the optimum cutoff value was a BRI ≥5.4. CONCLUSION: BRI was found to have a close relationship with arterial stiffness in overweight and obesity people. However, ABSI was weakly correlated with arterial stiffness, but not better than traditional anthropometric indices.

Initial experiences with a novel biodegradable device for percutaneous closure of atrial septal defects: From preclinical study to first-in-human experience.

OBJECTIVE: To evaluate the feasibility, safety, and effectiveness of a novel, absorbable atrial septal defect (ASD) closure device made of poly-l-lactic acid (PLLA) in a swine model of ASD and for the first time in humans. METHODS: A preclinical safety study was conducted using a swine model of ASD. In a clinical setting, five pediatric patients underwent ASD closure with the PLLA device with fluoroscopic and transthoracic echocardiography guidance. The procedural results and clinical outcomes at 1 day, 30 days, 3 months, and 6 months after closure were analyzed. RESULTS: The 24- and 36-month follow-up results of the preclinical study demonstrated that the PLLA device exhibited good endothelialization and degradability in the swine model. In the clinical study, successful device implantation was achieved in all five patients (median age, 3.6 years; range, 3.1-6.5 years). The mean defect size was (13.6 ± 2.7) mm. Follow-up at 30 days, 3 months, and 6 months was completed in all five cases. The complete defect closure rates with no residual shunt at 30 days, 3 months, and 6 months follow-up were 60% (3/5), 80% (4/5), and 80% (4/5), respectively. No device dislodgement, significant aortic valve or mitral valve regurgitation, new onset cardiac arrhythmia, or other adverse events were reported. CONCLUSION: The study results demonstrated that it is feasible to implant the PLLA device for closure of small to medium sized ASDs without significant residual shunts or severe adverse events in humans. The PLLA device exhibited good endothelialization and degradability in the swine model at 24 and 36 months. Further studies to evaluate long-term safety and effectiveness with the device in a large cohort of patients are warranted.

Study of biodegradable occluder of atrial septal defect in a porcine model.

OBJECTIVE: To evaluate the safety and feasibility of a modified poly(l-lactic acid) (PLLA) atrial septal defect (ASD) occluder. METHODS: Forty-five piglets were divided into two groups: an experimental group (n = 27) and a control group (n = 18). The experimental group underwent percutaneous implantation of a modified PLLA ASD device while the control group underwent percutaneous implantation of a widely used metal ASD device. X-ray imaging, transthoracic echocardiography (TTE), electrocardiogram (ECG), histopathology and electron microscopic examination were performed at 7 days, 1, 3, 6, and 12 months after implantation. RESULTS: Twenty-seven experimental piglets and 18 control piglets were all successfully implanted with modified biodegradable and metal ASD devices, respectively. While both devices exhibited very good occluding effects, the modified PLLA ASD devices were completely endothelialized at 3 months after implantation, and the endothelialization appeared to be more complete compared to the control group. Degradation of the PLLA devices was noted at 12 months follow-up with no loss of integrity at the atrial septum. CONCLUSION: This animal model with implanting of the occluders was effective and not associated with complications. The modified PLLA ASD devices are more controllable and practical than our previous devices. The implanted devices demonstrated good endothelialization and degradability in short and moderate term follow-up. Long-term studies are now underway to further evaluate the biodegradability of this novel device.

The feasibility of two anthropometric indices to identify metabolic syndrome, insulin resistance and inflammatory factors in obese and overweight adults.

OBJECTIVES: A body shape index (ABSI) and body roundness index (BRI) were reported to predict diabetes and hypertension in general population, but their validity was regularly questioned. The aim of this study was to evaluate whether ABSI and BRI are the best anthropometric indices to reflect metabolic syndrome (MetS), insulin resistance (IR), and inflammatory factors in obese and overweight Chinese adults. METHODS: Cross-sectional data on sociodemographic, lifestyle, anthropometric indices, clinical characteristics, and biochemical measurements were collected for 1442 Chinese obese and overweight adults. Logistic regression analysis examined the associations between anthropometric indices with incidences of MetS and IR in both sexes. Furthermore, the correlation between anthropometric indices and inflammatory factors was assessed. RESULTS: Multivariate regression analysis depicting BRI and waist circumference (WC) were associated significantly with MetS and IR. BRI had the highest odds ratios (ORs) for IR and WC had the highest ORs for MetS in all anthropometric indices. However, ABSI did not exhibit any association between the MetS and IR. The ABSI adjusted regression coefficients (ß values) were 0.403 for high-sensitivity C reactive protein, 0.077 for tumor necrosis factor-α, and 0.022 for interleukin-6. BRI and WC were also significantly associated with three inflammatory factors. Comparing the lowest with the highest quintile, BRI had the largest ORs for MetS (OR, 5.778; 95% confidence interval [CI], 2.954-11.303; P < 0.01) and IR (OR, 6.212; 95% CI, 2.912-13.250; P < 0.01). CONCLUSION: Only BRI and WC, not ABSI, can significantly determine the presence of MetS and IR. BRI showed the optimal capability to identify IR in obese and overweight population.

The circulating level of endothelial progenitor cells after transcatheter closure of congenital heart disease in children.

Data have shown that circulating endothelial progenitor cells (EPCs) closely correlate with the vascular endothelial layer state. The present study was designed to describe the evolution of EPCs in children before and 24 h after transcatheter closure surgery for occluding congenital heart disease. Three groups of patients were studied: the transcatheter closure of atrial septal defect (ASD) group (group 1), the transcatheter closure of patent ductus arteriosus (PDA) group (group 2), and the transcatheter closure of ventricular septal defect (VSD) group (group 3). The circulating EPC level was detected using flow cytometry measuring CD34 and kinase insert receptor double-positive mononuclear cells. The concentration of vascular endothelial growth factor (VEGF) was assessed by enzyme-linked immunosorbent assay. The fluoroscopy time was correctly recorded during the surgery. All of the data were collected before and 24 h after surgery. EPC level and VEGF concentration did not change significantly before and at 24 h after surgery in groups 1 and 2. In group 3, the level of circulating EPCs and VEGF concentration increased significantly 24 h after surgery. The fluoroscopy time in group 3 was significantly longer than in groups 1 and 2. The increased volume of EPCs and VEGF were positively correlated in group 3. Our results showed that transcatheter closure of PDA and ASD in children does not lead to increased circulating level of EPCs. Transcatheter closure of VSD may result in vascular endothelium injury as indicated by increased circulating EPC level.

[Characteristics of severely and critically ill children with 2009 influenza A (H1N1) virus infection].

OBJECTIVE: To analyze the clinical characteristics of severely and critically ill children with 2009 influenza A (H1N1) infection. METHOD: Clinical data of 150 cases with 2009 influenza A (H1N1) virus infection confirmed with the use of a real-time polymerase-chain-reaction assay on nasopharyngeal swab specimens were analyzed. RESULT: Among 150 severely and critically ill children with 2009 influenza A (H1N1) virus infection, 103 were male, 47 were female; the median age was 5 years, 81(55%) were 5 years of age or older; 21 (14%) had underlying chronic diseases. The most common presenting symptoms were fever (95%), cough (89%), vomiting (23%), wheezing (19%), abdominal pain (16%), lethargy (7%), seizures (6%), myalgia (6%), and diarrhea (6%). The common laboratory abnormalities were increased or decreased white blood cells counts (40%), elevated of CRP (33%), LDH (29%), CK (25%) and AST (19%). Clinical complications included pneumonia (65%), encephalopathy (12%), myocarditis (5%), encephalitis (1%) and myositis (1%). All patients had received antibiotics before admission or on admission; 73% of patients had received oseltamivir treatment, 23% of patients had received corticosteroids; 32 (21%) were admitted to an ICU, 13 patients were intubated and mechanically ventilated. Fourteen patients with dyspnea who were irresponsive to the treatment experienced bronchoalveolar lavage with flexible bronchoscopy, and the branching bronchial casts were removed in 5 patients. Totally 145 (97%) patients were discharged, five (3%) died, three previously healthy patients died from severe encephalopathy, one patient died from ARDS, one previously healthy patient died from secondary fungal meningitis. CONCLUSION: Severely and critically ill children with 2009 influenza A (H1N1) virus infection may occur mainly in older children without underlying chronic disease. The clinical spectrum and laboratory abnormality of the patients can have a wide range. Neurologic complications may be common and severe encephalopathy can lead to death in previously healthy children. Early use of bronchoalveolar lavage with flexible bronchoscopy may reduce death associated with pulmonary complications.