A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial.

BACKGROUND: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors. METHODS: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death). RESULTS: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse). CONCLUSION: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

OCT Angiography Use in Pregnancy: Branch Retinal Artery Occlusion Associated with Patent Foramen Ovale - A Case Report and Multimodal Analysis.

This case report is a multimodal analysis of a pregnant patient with branch retinal artery occlusion (BRAO) associated to patent foramen ovale (PFO). A 28-year-old woman presented at the clinic 20 h after an acute, painless black spot appearance in the inferior temporal visual field of the right eye (OD). At that time, she was 18 weeks pregnant and had no report of complications in her previous pregnancy. Best-corrected visual acuity was 1.0 in both eyes. Color fundus photo, perimetry, and OCT angiography were required. The results clearly showed an embolus in the superior nasal retinal arteriole, associated with a pallor in the distal retina. Patient was referred to a cardiologist and a transcranial Doppler with contrast indicated a right-to-left intracardiac shunt, confirmed by the presence of a PFO at the transesophageal echocardiography. Thrombophilic conditions were excluded. Enoxaparin 1 mg/kg was started and kept until the delivery. Now, a PFO surgical closure is on schedule. This case highlights the noteworthiness of considering PFO as a source of embolism for BRAO in young patients, the capability of OCTA as a dye-free method for use in pregnancy and emphasizes the importance of systemic evaluation in patients with BRAO.

Tumor mutation burden involving epigenetic regulatory genes and the RhoA GTPase predicts overall survival in nodal mature T-cell lymphomas.

Nodal mature T-cell lymphomas (nMTCL) comprises a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena, including mutations in genes that control DNA methylation and histone deacetylation, in addition to inactivating mutations in the RhoA GTPase, play a central role in its pathogenesis and constitute potential new targets for therapeutic intervention. Tumor mutational burden (TMB) reflects the process of clonal evolution, predicts response to anti-cancer therapies and has emerged as a prognostic biomarker in several solid neoplasms; however, its potential prognostic impact remains unknown in nMTCL. In this study, we conducted Sanger sequencing of formalin-fixed paraffin-embedded (FFPE) diagnostic tumor samples using a target-panel to search for recurrent mutations involving the IDH-1/IDH-2, TET-2, DNMT3A and RhoA genes in 59 cases of nMTCL. For the first time, we demonstrated that high-TMB, defined by the presence of ≥ two mutations involving the aforementioned genes, was associated with decreased overall survival in nMTCL patients treated with CHOP-like regimens. Additionally, high-TMB was correlated with bulky disease, lower overall response rate, and higher mortality. Future studies using larger cohorts may validate our preliminary results that indicate TMB as a potential molecular biomarker associated with adverse prognosis in nMTCL.

TET-2 mutations predict poor outcomes and are associated with unfavorable clinical-biological features in PTCL, not otherwise specified and angioimmunoblastic T-cell lymphoma in Brazilian patients.

INTRODUCTION: Nodal peripheral T-cell lymphomas [nPTCL] constitute a heterogeneous group of rare malignancies with aggressive biological behavior and poor prognosis. Epigenetic phenomena involving genes that control DNA-methylation and histone deacetylation play a central role in their pathogenesis. However, the mutational landscape involving epigenetic regulators has never been reported in Latin American patients and their prognostic impact remains controversial. PATIENTS AND METHODS: From 2000 to 2019, 59-Brazilian patients with nPTCL were eligible for screening mutations in the IDH-1, IDH-2, RHOA, TET-2 and DNMT3A genes by Sanger sequencing at Formalin-Fixed Paraffin-Embedded samples [FFPE] of diagnosis. We reported the frequency, distribution and potential prognosis of these mutations. RESULTS: With a median follow-up of 3.70 years, estimate 2-year OS and PFS were 57.1% and 49.2%, respectively. Mutations in the IDH-1 gene were not found, mutations in the IDH-2 occurred in 3.4% (2/59), RHOA in 23.7% (14/59), TET-2 in 50.8% (30/59) and DNMT3A in 62.7% (37/59). RHOA gene mutations were more frequent in PTCL, NOS and AITL (p= 0.06). Almost half of the patients had more than one mutation in concomitance, particularly RHOA-mut and TET-2-mut. Mutations in RHOA (p= 0.030) and TET-2 (p= 0.046) were associated with high-tumor burden. In the non-ALCL subgroup (PTCL, NOS and AITL) TET-2 mutations were associated with decreased 2-year PFS [HR: 2.22, p= 0.048]. Likewise with lower overall response rate [ORR] (p= 0.048) and unfavorable clinical features, as bulky disease (p= 0.012), ECOG ⩾ 2 (p= 0.032), B-symptoms (p= 0.012), ⩾ 2 extranodal sites compromised (p= 0.022) and high-risk Prognostic Index for T-cell lymphoma (p= 0.005). CONCLUSION: Mutations in RHOA, TET-2 and DNMT3A were frequent in Brazilian patients with nPTCL. TET-2 mutations were associated with lower ORR for CHOP-like chemotherapy, decreased PFS and unfavorable clinical-biological characteristics in non-ALCL (PTCL, NOS and AITL). Further studies using a larger cohort may validate our findings.

Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen-Results of a Real-Life Study From a Middle-Income Country.

BACKGROUND: Nodal peripheral T-cell lymphoma (nPTCL) constitute a heterogeneous group of neoplasms with aggressive behavior and poor-survival. They are more prevalent in Latin America and Asia, although data from Brazil are scarce. Its primary therapy is still controversial and ineffective. Therefore, we aim to describe clinical-epidemiological characteristics, outcomes, predictors factors for survival and compare the results of patients treated with CHOP and CHOEP regimens. METHODS: Retrospective, observational and single-center study involving 124 nPTCL patients from Brazil treated from 2000 to 2019. RESULTS: With a median follow-up of 23.7 months, the estimated 2-year overall survival (OS) and progression-free survival (PFS) were 59.2% and 37.3%, respectively. The median age was 48.5 years and 57.3% (71/124) were male, 81.5% (101/124) had B-symptoms, 88.7% (110/124) had advanced disease (stage III/IV) and 58.1% (72/124) presented International Prognostic Index (IPI) score ≥3, reflecting a real-life cohort. ORR to first-line therapy was 58.9%, 37.9% (N = 47) received CHOP-21 and 35.5% (N = 44) were treated with CHOEP-21; 30.1% (37/124) underwent to consolidation with involved field radiotherapy (IF-RT) and 32.3% (40/124) were consolidated with autologous hematopoietic stem cell transplantation (ASCT). The overall response rate (ORR) was similar for CHOP-21 (76.6%) and CHOEP-21 (65.9%), P = .259. Refractory disease was less frequent in the CHOEP-21 group (4.5% vs. 21.2%, P = .018). However, few patients were able to complete 6-cycles of CHOEP-21 (31.8%) than to CHOP-21 (61.7%), P = .003. Delays ≥2 weeks among the cycles of chemotherapy were more frequent for patients receiving CHOEP-21 (43.1% vs. 10.6%), P = .0004, as well as the toxicities, including G3-4 neutropenia (88% vs. 57%, P = .001), febrile neutropenia (70% vs. 38%, P = .003) and G3-4 thrombocytopenia (63% vs. 27%, P = .0007). The 2-year OS was higher for CHOP (78.7%) than CHOEP group (61.4%), P = .05, as well as 2-year PFS (69.7% vs. 25.0%, P < .0001). In multivariate analysis, high LDH (HR 3.38, P = .007) was associated with decreased OS. CR at first line (HR: 0.09, P < .001) and consolidation with ASCT (HR: 0.08, P = .015) were predictors of increased OS. CONCLUSION: In the largest cohort of nPTCL from Latin America, patients had poor survival and high rate of chemo-resistance. In our cohort, the addition of etoposide to the CHOP-21 backbone showed no survival benefit and was associated with high-toxicity and frequent treatment interruptions. Normal LDH values, obtaintion of CR and consolidation with ASCT were independent factors associated with better outcomes.

Optical Coherence Tomography Versus Intravascular Ultrasound and Angiography to Guide Percutaneous Coronary Interventions: The iSIGHT Randomized Trial.

[Figure: see text].

A stochastic variational framework for Recurrent Gaussian Processes models.

Gaussian Processes (GPs) models have been successfully applied to the problem of learning from sequential observations. In such context, the family of Recurrent Gaussian Processes (RGPs) have been recently introduced with a specifically designed structure to handle dynamical data. However, RGPs present a limitation shared by most GP approaches: they become computationally infeasible when facing very large datasets. In the present work, with the aim of improving scalability, we modify the original variational approach used with RGPs in order to enable inference via stochastic mini-batch optimization, giving rise to the Stochastic Recurrent Variational Bayes (S-REVARB) framework. We review recent related literature and comprehensively contextualize it with our approach. Moreover, we propose two learning procedures, the Local and Global S-REVARB algorithms, which prevent computational costs from scaling with the number of training samples. The global variant permits even greater scalability by also preventing the number of variational parameters from increasing with the training set, through the use of neural networks as sequential recognition models. The proposed framework is evaluated in the task of dynamical system identification for large scale datasets, a scenario not readily supported by the standard batch inference for RGPs. The promising results indicate that the S-REVARB framework opens up the possibility of applying powerful hierarchical recurrent GP-based models to massive sequential data.

Adaptive filtering with the self-organizing map: a performance comparison.

In this paper we provide an in-depth evaluation of the SOM as a feasible tool for nonlinear adaptive filtering. A comprehensive survey of existing SOM-based and related architectures for learning input-output mappings is carried out and the application of these architectures to nonlinear adaptive filtering is formulated. Then, we introduce two simple procedures for building RBF-based nonlinear filters using the Vector-Quantized Temporal Associative Memory (VQTAM), a recently proposed method for learning dynamical input-output mappings using the SOM. The aforementioned SOM-based adaptive filters are compared with standard FIR/LMS and FIR/LMS-Newton linear transversal filters, as well as with powerful MLP-based filters in nonlinear channel equalization and inverse modeling tasks. The obtained results in both tasks indicate that SOM-based filters can consistently outperform powerful MLP-based ones.

Condition monitoring of 3G cellular networks through competitive neural models.

We develop an unsupervised approach to condition monitoring of cellular networks using competitive neural algorithms. Training is carried out with state vectors representing the normal functioning of a simulated CDMA2000 network. Once training is completed, global and local normality profiles (NPs) are built from the distribution of quantization errors of the training state vectors and their components, respectively. The global NP is used to evaluate the overall condition of the cellular system. If abnormal behavior is detected, local NPs are used in a component-wise fashion to find abnormal state variables. Anomaly detection tests are performed via percentile-based confidence intervals computed over the global and local NPs. We compared the performance of four competitive algorithms [winner-take-all (WTA), frequency-sensitive competitive learning (FSCL), self-organizing map (SOM), and neural-gas algorithm (NGA)] and the results suggest that the joint use of global and local NPs is more efficient and more robust than current single-threshold methods.

Modeling and production of robot trajectories using the Temporal Parametrized Self Organizing Maps.

In this paper we proposed an unsupervised neural architecture, called Temporal Parametrized Self Organizing Map (TEPSOM), capable of learning and reproducing complex robot trajectories and interpolating new states between the learned ones. The TEPSOM combines the Self-Organizing NARX (SONARX) network, responsible for coding the temporal associations of the robotic trajectory, with the Parametrized Self-Organizing (PSOM) network, responsible for an efficient interpolation mechanism acting on the SONARX neurons. The TEPSOM network is used to model the inverse kinematics of the PUMA 560 robot during the execution of trajectories with repeated states. Simulation results show that the TEPSOM is more accurate than the SONARX in the reproduction of the learned trajectories.

A taxonomy for spatiotemporal connectionist networks revisited: the unsupervised case.

Spatiotemporal connectionist networks (STCNs) comprise an important class of neural models that can deal with patterns distributed in both time and space. In this article, we widen the application domain of the taxonomy for supervised STCNs recently proposed by Kremer (2001) to the unsupervised case. This is possible through a reinterpretation of the state vector as a vector of latent (hidden) variables, as proposed by Meinicke (2000). The goal of this generalized taxonomy is then to provide a nonlinear generative framework for describing unsupervised spatiotemporal networks, making it easier to compare and contrast their representational and operational characteristics. Computational properties, representational issues, and learning are also discussed, and a number of references to the relevant source publications are provided. It is argued that the proposed approach is simple and more powerful than the previous attempts from a descriptive and predictive viewpoint. We also discuss the relation of this taxonomy with automata theory and state-space modeling and suggest directions for further work.