How the COAPT trial affected the selection of patients with secondary mitral regurgitation undergoing transcatheter edge-to-edge repair: insights from the GIOTTO Registry.

Background: The impact of the COAPT results on clinical practice has not yet been investigated in large real-world cohort study. The aim of the study is to evaluate the potential impact of the COAPT trial by analyzing the temporal trends of baseline characteristics and outcome of secondary mitral regurgitation (SMR) patients undergoing MitraClip (MC) included in the GIOTTO registry.

Methods: The study population was divided into two groups, considering the enrolment before or after the COAPT publication.

Transcatheter management of residual mitral regurgitation after transcatheter edge-to-edge repair: a systematic review.

Background: Treatment of residual mitral regurgitation (MR) with different percutaneous devices after transcatheter edge-to-edge repair (TEER) has been reported as an alternative option to reclipping or surgery. This review aims at describing the different transcatheter strategies available and their results when managing residual MR after TEER.

Methods: A literature search was undertaken across Pubmed, ScienceDirect, SciELO, DOAJ, and Cochrane library databases, to identify article reporting patients with post-TEER residual MR managed by a transcatheter approach that did not involve only the implantation of new clips.

Development and validation of an LC-MS/MS multiplex assay for the quantification of bedaquiline, n-desmethyl bedaquiline, linezolid, levofloxacin, and clofazimine in dried blood spots.

Dried blood spot (DBS) assays to quantify novel and repurposed drugs for the treatment of rifampicin-resistant tuberculosis (RR-TB) would facilitate pharmacokinetic studies and therapeutic drug monitoring in low-middle income settings, considering their ease of application and simple sample storage requirements. We describe a DBS method for the simultaneous quantification of bedaquiline and metabolite N-desmethyl bedaquiline, linezolid, levofloxacin, and clofazimine. The analytes were extracted from the matrix and isolated by solid-phase extraction.

Transcatheter edge-to-edge repair in severe mitral regurgitation following acute myocardial infarction - aetiology-based analysis.

Aims: To evaluate the association between transcatheter edge-to-edge repair (TEER) and outcomes in patients with significant mitral regurgitation (MR) following acute myocardial infarction (MI), focusing on the aetiology of acute post-MI MR in high-risk surgical patients.

Methods And Results: The International Registry of MitraClip in Acute Mitral Regurgitation following Acute Myocardial Infarction (IREMMI) includes 187 patients with severe MR post-MI managed with TEER. Of these, 176 were included in the analysis, 23 (13%) patients had acute papillary muscle rupture (PMR) and 153 (87%) acute secondary MR.

Automatic 4D mitral valve segmentation from transesophageal echocardiography: a semi-supervised learning approach.

Performing automatic and standardized 4D TEE segmentation and mitral valve analysis is challenging due to the limitations of echocardiography and the scarcity of manually annotated 4D images. This work proposes a semi-supervised training strategy using pseudo labelling for MV segmentation in 4D TEE; it employs a Teacher-Student framework to ensure reliable pseudo-label generation. 120 4D TEE recordings from 60 candidates for MV repair are used.

Early Feasibility Study with the SATURN Transapical Mitral Valve Replacement Device.

Purpose: To report the outcomes of the early feasibility study of transapical transcatheter mitral valve replacement (TMVR) with the SATURN System (InnovHeart, Milano, Italy) to treat patients with severe functional mitral regurgitation.

Description: Five high surgical risk patients underwent transapical transcatheter mitral valve replacement with the SATURN System at a single center. One-year follow-up is complete for all patients.

Targeting TOP2A in Ovarian Cancer: Biological and Clinical Implications.

The enzyme topoisomerase II alpha (TOP2A) plays a critical role in DNA replication and cell proliferation, making it a promising target for cancer therapy. In epithelial ovarian cancer (EOC), TOP2A overexpression is associated with poor prognosis and resistance to conventional treatments. This review explores the biological functions of TOP2A in EOC and discusses its potential as a therapeutic target.

Weekly dihydroartemisinin-piperaquine versus monthly sulfadoxine-pyrimethamine for malaria chemoprevention in children with sickle cell anaemia in Uganda and Malawi (CHEMCHA): a randomised, double-blind, placebo-controlled trial.

Background: In many sub-Saharan African countries, it is recommended that children with sickle cell anaemia receive malaria chemoprevention with monthly sulfadoxine-pyrimethamine or daily proguanil as the standard of care. However, the efficacy of these interventions is compromised by high-grade antifolate resistance of Plasmodium falciparum and poor adherence. We aimed to compare the efficacy of weekly dihydroartemisinin-piperaquine and monthly sulfadoxine-pyrimethamine for the prevention of clinical malaria in children with sickle cell anaemia in areas with high-grade sulfadoxine-pyrimethamine resistance of P falciparum in Uganda and Malawi.

Pharmacokinetics of ethambutol and weight banded dosing in South African adults newly diagnosed with tuberculosis and HIV.

Ethambutol is used to treat tuberculosis (TB) in individuals living with HIV. Low concentrations of ethambutol have been reported in patients dosed with the World Health Organization (WHO)-recommended first-line regimen. We analyzed the pharmacokinetics of ethambutol in 61 HIV-positive individuals diagnosed with drug-sensitive TB enrolled in the tuberculosis and highly active antiretroviral therapy (TB-HAART) study.

Simulation-based training in ultrasound-guided regional anaesthesia for emergency physicians: insights from an Italian pre/post intervention study.

Background: Despite the importance of Ultrasound-guided Regional Anaesthesia (UGRA) in Emergency Medicine (EM), there is significant variability in UGRA training among emergency physicians. We recently developed a one-day (8 h), simulation-based UGRA course, specifically tailored to help emergency physicians to integrate these skills into their clinical practice.

Methods: In this pre/post intervention study, emergency physicians attended a course consisting of a 4-hour teaching on background knowledge and a practical part structured as follows: a scanning session on a healthy individual; a needling station with an ex-vivo model (turkey thighs); a simulation-based learning experience on local anaesthetic toxicity (LAST); a session on the UGRA simulator BlockSim™.

Analysis of Time-to-Positivity Data in Tuberculosis Treatment Studies: Identifying a New Limit of Quantification.

Background: The BACTEC Mycobacteria Growth Indicator Tube (MGIT) machine is the standard globally for detecting viable mycobacteria in patients' sputum. Samples are observed for no longer than 42 days, at which point the sample is declared 'negative' for tuberculosis (TB). This time to detection of bacterial growth, referred to as time-to-positivity (TTP), is increasingly of interest, not solely as a diagnostic tool but also as a continuous biomarker wherein change in TTP can be used for comparing the bactericidal activity of different TB treatments.

Advancing pharmacometrics in Africa-Transition from capacity development toward job creation.

Trained pharmacometricians remain scarce in Africa due to limited training opportunities, lack of a pharmaceutical product development ecosystem, and emigration to high-income countries. The Applied Pharmacometrics Training (APT) fellowship program was established to address these gaps and specifically foster job creation for talent retention. We review the APT program's progress over 3 years and encourage collaboration to enhance local clinical data analysis in Africa.

Determining Targets for Antiretroviral Drug Concentrations: A Causal Framework Illustrated With Pediatric Efavirenz Data From the CHAPAS-3 Trial.

Background: Determining a therapeutic window for maintaining antiretroviral drug concentrations within an appropriate range is required for identifying effective dosing regimens. The limits of this window are typically calculated using predictive models. We propose that target concentrations should instead be calculated based on counterfactual probabilities of relevant outcomes and describe a counterfactual framework for this.

The prognostic value of the Dandel's index in patients undergoing tricuspid transcatheter edge-to-edge repair.

Aims: Conventional parameters of right ventricular (RV) function are load-dependent and therefore do not accurately reflect contractility in patients with relevant tricuspid regurgitation (TR). RV adaptability to load has been characterized using the Dandel's index in patients with heart failure, but its prognostic value in patients undergoing tricuspid transcatheter edge-to-edge repair (T-TEER) has not been investigated so far.

Methods And Results: From the EuroTR registry (2019 to 2022), patients with complete datasets and a minimum of 2-years of follow-up were included.

Recoverability of causal effects under presence of missing data: a longitudinal case study.

Missing data in multiple variables is a common issue. We investigate the applicability of the framework of graphical models for handling missing data to a complex longitudinal pharmacological study of children with HIV treated with an efavirenz-based regimen as part of the CHAPAS-3 trial. Specifically, we examine whether the causal effects of interest, defined through static interventions on multiple continuous variables, can be recovered (estimated consistently) from the available data only.

Physiologically based pharmacokinetic modeling of drug-drug interactions between ritonavir-boosted atazanavir and rifampicin in pregnancy.

Ritonavir-boosted atazanavir (ATV/r) and rifampicin are mainstays of second-line antiretroviral and multiple anti-TB regimens, respectively. Rifampicin induces CYP3A4, a major enzyme involved in atazanavir metabolism, causing a drug-drug interaction (DDI) which might be exaggerated in pregnancy. Having demonstrated that increasing the dose of ATV/r from once daily (OD) to twice daily (BD) in non-pregnant adults can safely overcome this DDI, we developed a pregnancy physiologically based pharmacokinetic (PBPK) model to explore the impact of pregnancy.

The impact of physiological state and environmental stress on bacterial load estimation methodologies for Mycobacterium tuberculosis.

When processed in solid or liquid medium, tuberculosis patient samples yield different proportions of a heterogenous bacterial community over the duration of treatment. We aimed to derive a relationship between methodologies for bacterial load determination and assess the effect of the growth phase of the parent culture and its exposure to stress on the results. Mycobacterium tuberculosis H37Rv was grown with and without antibiotic (isoniazid or rifampicin) and sampled on day 0, 3, 11 and 21 of growth in broth culture.

Causal Inference for Continuous Multiple Time Point Interventions.

There are limited options to estimate the treatment effects of variables which are continuous and measured at multiple time points, particularly if the true dose-response curve should be estimated as closely as possible. However, these situations may be of relevance: in pharmacology, one may be interested in how outcomes of people living with-and treated for-HIV, such as viral failure, would vary for time-varying interventions such as different drug concentration trajectories. A challenge for doing causal inference with continuous interventions is that the positivity assumption is typically violated.