Clinical Outcomes at 1 Year Following Transcatheter Left Atrial Appendage Occlusion in the United States

ObjectivesThe aim of this study was to report 1-year clinical outcomes following commercial transcatheter left atrial appendage occlusion (LAAO) in the United States.BackgroundThe National Cardiovascular Data Registry LAAO Registry was initiated to meet a condition of Medicare coverage and allow the assessment of clinical outcomes. The 1-year rates of thromboembolic events after transcatheter LAAO in such a large cohort of “real-world” patients have not been previously reported.MethodsPatients entered into the National Cardiovascular Data Registry LAAO Registry for a Watchman procedure between January 1, 2016, and December 31, 2018, were included. The primary endpoint was ischemic stroke. Key secondary endpoints included the rate of ischemic stroke or systemic embolism, mortality, and major bleeding. Major bleeding was defined as any bleeding requiring hospitalization, and/or causing a decrease in hemoglobin level > 2g/dL, and/or requiring blood transfusion that was not hemorrhagic stroke. The Kaplan-Meier method was used for 1-year estimates of cumulative event rates.ResultsThe study population consisted of 36,681 patients. The mean age was 76.0 ± 8.1 years, the mean CHA₂DS₂-VASc score was 4.8 ± 1.5, and the mean HAS-BLED score was 3.0 ± 1.1. Prior stroke was present in 25.5%, clinically relevant bleeding in 69.5%, and intracranial bleeding in 11.9%. Median follow-up was 374 days (IQR: 212-425 days). The Kaplan-Meier–estimated 1-year rate of ischemic stroke was 1.53% (95% CI: 1.39%-1.69%), the rate of ischemic stroke or systemic embolism was 2.19% (95% CI: 2.01%-2.38%), and the rate of mortality was 8.52% (95% CI: 8.19%-8.87%). The 1-year estimated rate of major bleeding was 6.93% (95% CI: 6.65%-7.21%). Most bleeding events occurred between discharge and 45 days following the procedure.ConclusionsThis study characterizes important outcomes in a national cohort of patients undergoing transcatheter LAAO in the United States. Clinicians and patients can integrate these data in shared decision making when considering this therapy.     

轴向载荷分担比指导外固定器动力化的临床应用

目的:探讨轴向载荷分担比用于胫腓骨骨干骨折术后指导外固定器轴向动力化促进骨折愈合的有效性。方法:选取外固定器治疗的胫腓骨骨干骨折患者100例,随机分为观察组50例,对照组50例。观察组在轴向载荷分担比指导下行外固定器轴向动力化治疗,对照组未行动力化,随访比较两组的治疗效果。结果:所有患者均获随访,随访时间4～12个月,平均6.5个月,治疗期间所有患者均未出现外固定针断裂、松动及再骨折等并发症,观察组1例骨搬移患者轴向载荷分担比5%,X线片显示骨折断端有连续性骨痂通过,拆除外固定器连接杆后发生移位,恢复原数值行轴向加压再动力化,现已愈合。观察组除外1例骨搬移患者,其余49例患者外固定器固定时间为[(24.4±4.7)周],骨折临床愈合时间为[(22.4±4.7)周],与对照组50例患者外固定器固定时间[(29.3±5.6)周],骨折临床愈合时间[(27.3±5.6)周]比较,显著减少(P0.05)。结论:外固定器轴向载荷分担比指导胫腓骨骨干骨折外固定术后轴向动力化可以加速骨折愈合,但不适合骨搬移截骨端已硬化患者。     

Correcting forensic DNA errors

DNA mixture interpretation can produce opposing conclusions by qualified forensic analysts, even within the same laboratory. The long-delayed publication of the National Institutes of Standards and Technology (NIST) study of 109 North American crime laboratories in this journal demonstrates this most clearly. This latest study supports earlier work that shows common methods such as the Combined Probability of Inclusion (CPI) have wrongly included innocent people as contributors to DNA mixtures. The 2016 President's Council of Advisors on Science and Technology report concluded, “In summary, the interpretation of complex DNA mixtures with the CPI statistic has been an inadequately specified—and thus inappropriately subjective—method. As such, the method is clearly not foundationally valid” [7]. The adoption of probabilistic genotyping by many laboratories will certainly prevent some of these errors from occurring in the future, but the same laboratories that produced past errors can also now review old cases with their new software—without additional bench work. It is critical that laboratories adopt procedures and policies to do this.     

Identification of key genes and pathways in discoid lupus skin via bioinformatics analysis

Discoid lupus erythematosus (DLE) is the most common skin manifestation of lupus; however, the molecular mechanisms underlying DLE remain unknown. Therefore, we aimed to identify key differentially expressed genes (DEGs) in discoid lupus skin and investigate their potential pathways.To identify candidate genes involved in the occurrence and development of the disease, we downloaded the microarray datasets {"type":"entrez-geo","attrs":{"text":"GSE52471","term_id":"52471"}}GSE52471 and {"type":"entrez-geo","attrs":{"text":"GSE72535","term_id":"72535"}}GSE72535 from the Gene Expression Database (GEO). DEGs between discoid lupus skin and normal controls were selected using the GEO2R tool and Venn diagram software (http://bioinformatics.psb.ugent.be/webtools/Venn/). The Database for Annotation, Visualization, and Integrated Discovery (DAVID), Enrichr, and Cytoscape ClueGo were used to analyze the Kyoto Encyclopedia of Gene and Genome pathways and gene ontology. Protein-protein interactions (PPIs) of these DEGs were further assessed using the Search Tool for the Retrieval Interacting Genes version 10.0.Seventy three DEGs were co-expressed in both datasets. DEGs were predominantly upregulated in receptor signaling pathways of the immune response. In the PPI network, 69 upregulated genes were selected. Furthermore, 4 genes (CXCL10, ISG15, IFIH1, and IRF7) were found to be significantly upregulated in the RIG-I-like receptor signaling pathway, from analysis of Enrichr and Cytoscape ClueGo.The results of this study may provide new insights into the potential molecular mechanisms of DLE. However, further experimentation is required to confirm these findings.     

Interventions to respond to COVID 19 pandemic in Mumbai and way forward

With the emergence of COVID 19 pandemic, the approach used by Municipal Corporation of Greater Mumbai (MCGM) was based on all guidelines of COVID 19 prepared by Ministry of Health and Family Welfare (MoHFW). However, Mumbai undertook a special innovate model used in the mission Mumbai – Dharavi for COVID 19. Additionally, MCGM undertook a proactive approach of “chasing the virus” with its 4Ts: 1. Tracing 2. Tracking 3. Testing 4. Treating in high-risk slum clusters and it reflects the result of declining the incidence and case fatality due to COVID 19. Establishing public health surge capacities which include active surveillance, contact-tracing and follow-up besides early detection, isolation and management of cases are important steps for fighting the COVID 19 pandemic. Collaborating with all partners and setting up a Task force for establishing clinical management protocols was unmissable.     

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment‐resistant depressed patients—one of several targets under investigation—has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.     

Outcomes of coronary artery bypass grafting in patients with heart failure with a midrange ejection fraction

BackgroundCoronary artery bypass grafting (CABG) improves survival in patients with heart failure and severely reduced left ventricular systolic function (LVEF). Limited data exist regarding adverse cardiovascular event rates after CABG in patients with heart failure with midrange ejection fraction (HFmrEF; LVEF > 40% and < 55%).MethodsWe analyzed data on isolated CABG patients from the Veterans Affairs national database (2010-2019). We stratified patients into control (normal LVEF and no heart failure), HFmrEF, and heart failure with reduced LVEF (HFrEF) groups. We compared all-cause mortality and heart failure hospitalization rates between groups with a Cox model and recurrent events analysis, respectively.ResultsIn 6533 veterans, HFmrEF and HFrEF was present in 1715 (26.3%) and 566 (8.6%) respectively; the control group had 4252 (65.1%) patients. HFrEF patients were more likely to have diabetes mellitus (59%), insulin therapy (36%), and previous myocardial infarction (31%). Anemia was more prevalent in patients with HFrEF (49%) as was a lower serum albumin (mean, 3.6 mg/dL). Compared with the control group, a higher risk of death was observed in the HFmrEF (hazard ratio [HR], 1.3 [1.2-1.5)] and HFrEF (HR, 1.5 [1.2-1.7]) groups. HFmrEF patients had the higher risk of myocardial infarction (subdistribution HR, 1.2 [1-1.6]; P = .04). Risk of heart failure hospitalization was higher in patients with HFmrEF (HR, 4.1 [3.5-4.7]) and patients with HFrEF (HR, 7.2 [6.2-8.5]).ConclusionsHeart failure with midrange ejection fraction negatively affects survival after CABG. These patients also experience higher rates myocardial infarction and heart failure hospitalization.