Effect of antecedent statin usage on conduction disturbances and arrhythmias after transcatheter aortic valve replacement.

BACKGROUND: Post-transcatheter aortic valve replacement (TAVR) conduction disturbances and atrial fibrillation (AF) are associated with markedly worse short- and long-term prognosis. Statins have multiple pleotropic effects that may be beneficial in mitigating the risk of these procedural complications as has been found for various other cardiac procedures and surgeries. METHODS: Data were retrospectively collected on consecutive patients in the Yale New Haven Health TAVR Registry who did not have a prior pacemaker, had at least 1 pre- and post-TAVR electrocardiogram, and did not have a change to their statin regimen during the index hospitalization. The primary endpoint was the composite of new pacemaker placement, new AF, and other new conduction disturbances evaluated at 7 days post-TAVR. RESULTS: Between, July 2012 and August 2019, 612 patients met inclusion criteria. Of these, 162 patients were not on antecedent statins, and 450 were (28 low-intensity, 225 moderate-intensity, and 197 high-intensity). After 1:1 propensity matching, 99 patients on moderate-/high-intensity statins were matched to 99 patients not on antecedent statins. At 7 days, there was no significant difference in the occurrence of the primary endpoint (57 % statin users vs 46 % non-statin users; p = 0.16). There was a trend toward increased conduction disturbances 7 days after TAVR in statin users (56 % vs 42 %; p = 0.07), but rates of AF (5 % vs 8 %; p = 0.39) and pacemaker placement (9 % vs 15 %; p = 0.20) were numerically lower in statin users. There was no significant difference in persistent conduction disturbances (21 % vs 18 %; p = 0.59). CONCLUSIONS: Statins do not appear to reduce the risk of post-TAVR AF or conduction abnormalities in this small retrospective study.

Integrated Transcriptome and Metabolomics to Reveal the Mechanism of Adipose Mesenchymal Stem Cells in Treating Liver Fibrosis.

Liver fibrosis (LF) is a late-stage process observed in various chronic liver diseases with bile and retinol metabolism closely associated with it. Adipose-derived mesenchymal stem cells (ADMSCs) have shown significant therapeutic potential in treating LF. In this study, the transplantation of ADMSCs was applied to a CCl4-induced LF model to investigate its molecular mechanism through a multi-omics joint analysis. The findings reveal that ADMSCs effectively reduced levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), gamma-glutamyltransferase (GGT), Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and α-Smooth muscle actin (α-SMA), thereby mitigating liver lesions, preventing liver parenchymal necrosis, and improving liver collagen deposition. Furthermore, 4751 differentially expressed genes (DEGs) and 270 differentially expressed metabolites (DMs) were detected via transcriptome and metabolomics analysis. Conjoint analysis showed that ADMSCs up-regulated the expression of Cyp7a1, Baat, Cyp27a1, Adh7, Slco1a4, Aldh1a1, and Adh7 genes to promote primary bile acids (TCDCA: Taurochenodeoxycholic acid; GCDCA: Glycochenodeoxycholic acid; GCA: glycocholic acid, TCA: Taurocholic acid) synthesis, secretion and retinol metabolism. This suggests that ADMSCs play a therapeutic role in maintaining bile acid (BA) homeostasis and correcting disturbances in retinol metabolism.

Rapid quantification of the surface overflow and underground infiltration in sewer pipes based on computer vision and continuous optimization.

The overloading of the sewer network caused by unwarranted infiltration of stormwater may lead to waterlogging and environmental pollution. The accurate identification of infiltration and surface overflow is essential to predict and reduce these risks. To retrieve the limitations of infiltration estimation and the failure of surface overflow perception using the common stormwater management model (SWMM), a surface overflow and underground infiltration (SOUI) model is proposed to estimate the infiltration and overflow. First, the precipitation, water level of the manhole, surface water depth and images of the overflowing point, and volume at the outfall are collected. Then, the surface waterlogging area is identified based on computer vision to reconstruct the local digital elevation model (DEM) by spatial interpolation, and the relationship between the waterlogging depth, area and volume is established to identify the real-time overflow. Next, a continuous genetic algorithm optimization (CT-GA) model is proposed for the underground sewer system to determine the inflow rapidly. Finally, surface and underground flow estimations are combined to perceive the state of the urban sewer network accurately. The results show that, compared with the common SWMM simulation, the accuracy of the water level simulation is improved by 43.5% during the rainfall period, and the time cost of the computational optimization is reduced by 67.5%. The proposed method can effectively diagnose the operation state and overflow risk of the sewer networks in real time during rainfall seasons.

A novel multi-strategy hydrological feature extraction (MHFE) method to improve urban waterlogging risk prediction, a case study of Fuzhou City in China.

Reliable hydrological data ensure the precision of the urban waterlogging simulation. To reduce the simulation error caused by insufficient basic data, a multi-strategy method (MHFE) for extracting hydrological features is proposed, which includes land use/land cover (LULC) extraction (LE) and digital elevation model (DEM) reconstruction (DR). First, the high-resolution remote image, satellite DEM, precipitation, flood points and depth, and planned LULC were collected. Second, the buildings, roads, and other areas of the satellite image were segmented using the U-Net model, and the LULC data with drainage features were extracted by combining the segmentation result with the planned LULC and drainage data. Then, the terrain features of the road were enhanced to construct high-precision DEM based on the fusion of multi-source data, such as elevation points, LULC, and satellite DEM. Finally, the waterlogging model was implemented under different return periods of rainfalls and typhoon rainfall to obtain the waterlogging distribution and water depth. The simulation results were compared with historical waterlogging event data and water depth observations. The results indicated that the proposed method significantly improved the accuracy of the simulation. In terms of identifying the waterlogging points, the average F1 score increased by 0.36, 0.20, and 0.07 compared to the raw model and the single LE and DR methods, respectively. In terms of water depth simulation, the average Nash-Sutcliffe efficiency (NSE) was increased from -0.24 to 0.86, with DR and LE contributing to 79.1 % and 20.9 %, respectively. The principal contribution and novelty of this paper is to explore the generic method that enhance the hydrological data, and the findings of this study improved the performance of urban waterlogging simulation.

Impact of New-Onset Conduction Disturbances following Transcatheter Aortic Valve Replacement on Outcomes: A Single-Center Study.

Background: Transcatheter aortic valve replacement (TAVR) is known to increase the incidence of conduction disturbances compared to surgical aortic valve replacement; however, there are limited data on the impact and duration of these conduction disturbances on longer term outcomes. Objective: To determine the differential impact of persistent versus nonpersistent new-onset conduction disturbances on TAVR-related complications and outcomes. Methods: This is a single-center retrospective analysis of 927 consecutive patients with aortic stenosis who underwent TAVR at Yale New Haven Hospital from July 2012 to August 2019. Patients with new-onset conduction disturbances within 7 days following TAVR were selected for this study. Persistent and nonpersistent disturbances were, respectively, defined as persisting or not persisting on all patient ECGs for up to 1.5 years after TAVR or until death. Results: Within 7 days after TAVR, conduction disturbances occurred in 42.3% (392/927) of the patients. Conduction disturbances persisted in 150 (38%) patients and did not persist in 187 (48%) patients, and 55 (14%) patients were excluded for having mixed (both persistent and nonpersistent) disturbances. Compared with nonpersistent disturbances, patients with persistent disturbances were more likely to receive a PPM within 7 days after the TAVR procedure (46.0% versus 4.3%, p < 0.001) and had a greater unadjusted 1-year cardiac-related and all-cause mortality risk (HR 2.54, p=0.044 and HR 1.90, p=0.046, respectively). Conclusion: Persistent conduction disturbances were associated with a greater cardiac and all-cause mortality rate at one year following TAVR. Future research should investigate periprocedural factors to reduce persistent conduction disturbances and outcomes beyond one year follow-up.

Colchicine and high-intensity rosuvastatin in the treatment of non-critically ill patients hospitalised with COVID-19: a randomised clinical trial.

OBJECTIVE: To evaluate the effect of colchicine and high-intensity rosuvastatin in addition to standard of care on the progression of COVID-19 disease in hospitalised patients. DESIGN: A pragmatic, open-label, multicentre, randomised controlled trial conducted from October 2020 to September 2021. Follow-up was conducted at 30 and 60 days. The electronic medical record was used at all stages of the trial including screening, enrolment, randomisation, event ascertainment and follow-up. SETTING: Four centres in the Yale New Haven Health System. PARTICIPANTS: Non-critically ill hospitalised patients with COVID-19. INTERVENTIONS: Patients were randomised 1:1 to either colchicine plus high-intensity rosuvastatin in addition to standard of care versus standard of care alone. Assigned treatment was continued for the duration of index hospitalisation or 30 days, whichever was shorter. PRIMARY AND SECONDARY OUTCOME MEASURES: The prespecified primary endpoint was progression to severe COVID-19 disease (new high-flow or non-invasive ventilation, mechanical ventilation, need for vasopressors, renal replacement therapy or extracorporeal membrane oxygenation, or death) or arterial/venous thromboembolic events (ischaemic stroke, myocardial infarction, deep venous thrombosis or pulmonary embolism) evaluated at 30 days. RESULTS: Among the 250 patients randomised in this trial (125 to each arm), the median age was 61 years, 44% were women, 15% were Black and 26% were Hispanic/Latino. As part of the standard of care, patients received remdesivir (87%), dexamethasone (92%), tocilizumab (18%), baricitinib (2%), prophylactic/therapeutic anticoagulation (98%) and aspirin (91%). The trial was terminated early by the data and safety monitoring board for futility. No patients were lost to follow-up due to electronic medical record follow-up. There was no significant difference in the primary endpoint at 30 days between the active arm and standard of care arm (15.2% vs 8.8%, respectively, p=0.17). CONCLUSIONS: In this small, open-label, randomised trial of non-critically ill hospitalised patients with COVID-19, the combination of colchicine and rosuvastatin in addition to standard of care did not appear to reduce the risk of progression of COVID-19 disease or thromboembolic events, although the trial was underpowered due to a lower-than-expected event rate. The trial leveraged the power of electronic medical records for efficiency and improved follow-up and demonstrates the utility of incorporating electronic medical records into future trials. TRIAL REGISTRATION: NCT04472611.

The early predictive effect of low expression of the ITGA4 in colorectal cancer.

Background: The early diagnosis of colorectal cancer (CRC) is very important for the prognosis of patients. It has been suggested that the cytosine-phosphate-guanine (CpG) island of itga4 is highly methylated in colorectal adenoma cell lines AA/C1, Vaco 235 and so on. So the purpose of our study is to explore the diagnostic accuracy and related mechanism of integrin alpha 4 (ITGA4) in early CRC. Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the relationship between the expression of ITGA4 and the clinicopathological features and the overall survival rate of the disease. Then, the interaction protein and function enrichment region of ITGA4 were analyzed. Finally, the infiltration of related immune cells was analyzed. Results: Compared with normal tissues, the expression of ITGA4 in colon adenocarcinoma and rectum adenocarcinoma (COAD-READ) tumor tissues was lower (P<0.05). The overall survival rate of COAD-READ patients with low ITGA4 level was lower than that of patients with high ITGA4 expression (P<0.05), and expression of ITGA4 had a more significant predictive effect in the early stage of tumor development. The results of protein network and enrichment analysis suggested that ITGA4 was closely related to ITGB2 and might be involved in the inflammatory reaction and inflammatory tumor transformation process in the carcinogenesis of inflammatory bowel disease (IBD), which was verified by another independent sequence. In terms of immune infiltration, the expression level of ITGA4 was positively correlated with the infiltration level of intestinal macrophages (Th17), immature dendritic cells (IDC), dendritic cells (DC), mast cells, and eosinophils in COAD-READ, and significantly negatively correlated with CD56bright natural killer (NK) cells. Conclusions: The low expression of ITGA4 was related to the poor prognosis of COAD-READ. Findings showed that ITGA4 might participate in the inflammatory reaction and inflammatory tumor transformation process in the carcinogenesis of IBD, and that ITGA4 was related to the infiltration of immune cells, macrophages, syndactyls, and CD56bright NK cells. The expression of ITGA4 could be used as an early predictor of CRC. However, the mechanism of ITGA4 promoting tumor progression in CRC still needs further research.

Short Term Real-Time Rolling Forecast of Urban River Water Levels Based on LSTM: A Case Study in Fuzhou City, China.

Water level management is an important part of urban water system management. In flood season, the river should be controlled to ensure the ecological and landscape water level. In non-flood season, the water level should be lowered to ensure smooth drainage. In urban areas, the response of the river water level to rainfall and artificial regulation is relatively rapid and strong. Therefore, building a mathematical model to forecast the short-term trend of urban river water levels can provide a scientific basis for decision makers and is of great significance for the management of urban water systems. With a focus on the high uncertainty of urban river water level prediction, a real-time rolling forecast method for the short-term water levels of urban internal rivers and external rivers was constructed, based on long short-term memory (LSTM). Fuzhou City, China was used as the research area, and the forecast performance of LSTM was analyzed. The results confirm the feasibility of LSTM in real-time rolling forecasting of water levels. The absolute errors at different times in each forecast were compared, and the various characteristics and causes of the errors in the forecast process were analyzed. The forecast performance of LSTM under different rolling intervals and different forecast periods was compared, and the recommended values are provided as a reference for the construction of local operational forecast systems.

Tiaochang Xiaoliu Decoction Granules prevent the recurrence of colorectal adenoma: a study protocol for a randomized controlled trial.

BACKGROUND: With the changes in lifestyle and diet, the incidence and mortality of colorectal cancer (CRC) is increasing in China. CRC mainly develops from colorectal adenomas (CRAs). There is a lack of chemopreventative drugs with definite efficacy for CRAs. Tiaochang Xiaoliu Decoction (TXD) was developed by Professor Yunjian Luo and has been used clinically over the last ten years for the prevention of CRA recurrence. To facilitate its clinical use, TXD was further standardized and produced as "Tiaochang Xiaoliu Decoction Granules (TXDG)". A study was designed to investigate the preventive effects of TXDG on the recurrence of CRA. METHODS: A randomized, double-blinded, controlled, and multi-center experiment is proposed to assess the effectiveness and safety of TXDG. Patients with CRAs (after complete polypectomy under colonoscopy) will be randomly divided into two groups, one will be treated with TXDG (the TXDG group) and the other will be treated with a TXDG mimetic agent (the TXDG mimetic group). The patients will be treated for 6 months and followed up for 3 years. Follow-up colonoscopy is expected to be carried out within 1 to 3 years after the baseline examinations. The primary outcome measure is adenoma detection rate within 1 to 3 years. The secondary outcome measures are the number, location, and pathology of the adenomas, and the polyp detection rate. DISCUSSION: Reliable objective evidence will be provided to evaluate the efficacy and safety of TXDG as an accessorial therapy for CRA occurrence in post-polypectomy patients. TRIAL REGISTRATION: ChiCTR2000035257.