Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support

Surgical management of tetralogy of Fallot (TOF) results in anatomic and functional abnormalities in the majority of patients. Although right ventricular volume load due to severe pulmonary regurgitation can be tolerated for many years, there is now evidence that the compensatory mechanisms of the right ventricular myocardium ultimately fail and that if the volume load is not eliminated or reduced by pulmonary valve replacement the dysfunction might be irreversible. Cardiovascular magnetic resonance (CMR) has evolved during the last 2 decades as the reference standard imaging modality to assess the anatomic and functional sequelae in patients with repaired TOF. This article reviews the pathophysiology of chronic right ventricular volume load after TOF repair and the risks and benefits of pulmonary valve replacement. The CMR techniques used to comprehensively evaluate the patient with repaired TOF are reviewed and the role of CMR in supporting clinical decisions regarding pulmonary valve replacement is discussed

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021

Repair of fresh patellar tendon rupture: tension regulation at the suture line

The reported complications of the repaired patellar tendon have been attributed to the influence of the mechanical environment on the healing process. This study postulates that the healing complications can be minimised through tension regulation at the suture line using an absorbable reinforcement device. Twelve patients with fresh patellar tendon rupture were included in the study. They were prospectively followed up for an average period of 45 months. The patients resumed their pre-injury activities at an average of 6.1 months. The active knee movement averaged 0–154.6° compared to 0–156.7° in the contralateral knee. Radiologically no patella alta, patella baja or degenerative changes in the patellofemoral joints were noted. The results support use of the absorbable reinforcement device for tension regulation at the suture line

In Vivo pH Imaging with 99mTc-pHLIP

PURPOSE: A novel molecular imaging agent has been developed recently which stains tissues of low extracellular pH (pH (low) insertion peptide, pHLIP(®)). A pH-dependent process of peptide folding and insertion into cell membranes has been found in vitro. Targeting of acidic solid tumours has been demonstrated in vivo using fluorescence and PET labels. Here we present proof of feasibility studies of pHLIP with a SPECT label, (99m)Tc-AH114567, with focus on preclinical efficacy and imageability. PROCEDURES: LLC, LNCaP and PC-3 tumour xenografts were grown in mice and characterised by the angiogenesis marker (99m)Tc-NC100692 and by extracellular pH measurements with (31)P-MRS of 3-aminopropyl phosphonate. Biodistribution was assessed and CT/SPECT imaging performed. Oral administration of bicarbonate served as control. RESULTS AND CONCLUSION: (99m)Tc-AH114567 can be obtained via a robust synthesis with good radiolabelling profile and improved formulation. The tracer retains the pH-dependent ability to insert into membranes and to target tumours with similar pharmacokinetics and efficacy that had been demonstrated earlier for pHLIP with optical or (64)Cu PET labels. Despite the inherent challenges of SPECT compared to optical and PET imaging e.g. in terms of lower sensitivity, (99m)Tc-AH114567 shows adequate image quality and contrast. The main development need for transitioning SPECT labelled pHLIP into the clinic is more rapid background signal reduction which will be the focus of a subsequent optimization study