Treatment of Later Humoral Rejection with Anti-CD20 Monoclonal Antibody Rituximab: A Single Centre Experience

Humoral or vascular rejection is a B cell-mediated production of immunoglobulin (Ig) G antibody against a transplanted organ that results in immune complex deposition on the vascular endothelium, activation of the complement cascade, production of endothelial dysfunction and regional ischaemic injury

Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure.

Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF is scant. Eccentric (ECC) cycling is a novel exercise modality which may be particularly suited to patients with CHF, but the acute impacts of ECC on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC increased baseline artery diameter (pre: 4.0±0.8mm vs post: 4.2±0.7mm, P=0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for the decrease in FMD post-ECC was no longer significant. No changes were apparent after CON. Neither ECC nor CON resulted in changes to any platelet function measures (all P>0.05). These results suggest both ECC and CON cycling at a moderate intensity and short duration can be performed by patients with HFrEF, without detrimental impacts on vascular or platelet function

Evaluation of an Artificial Intelligence Coronary Artery Calcium Scoring Model from Computed Tomography

OBJECTIVES: Coronary artery calcium (CAC) scores derived from computed tomography (CT) scans are used for cardiovascular risk stratification. Artificial intelligence (AI) can assist in CAC quantification and potentially reduce the time required for human analysis. This study aimed to develop and evaluate a fully automated model that identifies and quantifies CAC. METHODS: Fully convolutional neural networks for automated CAC scoring were developed and trained on 2439 cardiac CT scans and validated using 771 scans. The model was tested on an independent set of 1849 cardiac CT scans. Agatston CAC scores were further categorised into five risk categories (0, 1–10, 11–100, 101–400, and > 400). Automated scores were compared to the manual reference standard (level 3 expert readers). RESULTS: Of 1849 scans used for model testing (mean age 55.7 ± 10.5 years, 49% males), the automated model detected the presence of CAC in 867 (47%) scans compared with 815 (44%) by human readers (p = 0.09). CAC scores from the model correlated very strongly with the manual score (Spearman’s r = 0.90, 95% confidence interval [CI] 0.89–0.91, p < 0.001 and intraclass correlation coefficient = 0.98, 95% CI 0.98–0.99, p < 0.001). The model classified 1646 (89%) into the same risk category as human observers. The Bland–Altman analysis demonstrated little difference (1.69, 95% limits of agreement: −41.22, 44.60) and there was almost excellent agreement (Cohen’s κ = 0.90, 95% CI 0.88–0.91, p < 0.001). Model analysis time was 13.1 ± 3.2 s/scan. CONCLUSIONS: This artificial intelligence–based fully automated CAC scoring model shows high accuracy and low analysis times. Its potential to optimise clinical workflow efficiency and patient outcomes requires evaluation. KEY POINTS: • Coronary artery calcium (CAC) scores are traditionally assessed using cardiac computed tomography and require manual input by human operators to identify calcified lesions. • A novel artificial intelligence (AI)–based model for fully automated CAC scoring was developed and tested on an independent dataset of computed tomography scans, showing very high levels of correlation and agreement with manual measurements as a reference standard. • AI has the potential to assist in the identification and quantification of CAC, thereby reducing the time required for human analysis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00330-022-09028-3

Is the Soleus a Sentinel Muscle for Impaired Aerobic Capacity in Heart Failure?

Purpose: Skeletal muscle wasting is well documented in chronic heart failure (CHF). This article provides a more detailed understanding of the morphology behind this muscle wasting and the relation between muscle morphology, strength, and exercise capacity in CHF. We investigated the effect of CHF on lower limb lean mass, detailed muscle–tendon architecture of the individual triceps surae muscles (soleus (SOL), medial gastrocnemius, and lateral gastrocnemius) and how these parameters relate to exercise capacity and strength. Methods: Eleven patients with CHF and 15 age-matched controls were recruited. Lower limb lean mass was assessed by dual energy x-ray absorptiometry and the architecture of skeletal muscle and tendon properties by ultrasound. Plantarflexor strength was assessed by dynamometry. Results: Patients with CHF exhibited approximately 25% lower combined triceps surae volume and physiological cross-sectional area (PCSA) compared with those of control subjects (P < 0.05), driven in large part by reductions in the SOL. Only the SOL volume and the SOL and medial gastrocnemius physiological cross-sectional area were statistically different between groups after normalizing to lean body mass and body surface area, respectively. Total lower limb lean mass did not differ between CHF and control subjects, further highlighting the SOL specificity of muscle wasting in CHF. Moreover, the volume of the SOL and plantarflexor strength correlated strongly with peak oxygen uptake (V˙O2peak) in patients with CHF. Conclusions: These findings suggest that the SOL may be a sentinel skeletal muscle in CHF and provide a rationale for including plantarflexor muscle training in CHF care

Gait analysis in chronic heart failure: The calf as a locus of impaired walking capacity

Reduced walking capacity, a hallmark of chronic heart failure (CHF), is strongly correlated with hospitalization and morbidity. The aim of this work was to perform a detailed biomechanical gait analysis to better identify mechanisms underlying reduced walking capacity in CHF. Inverse dynamic analyses were conducted in CHF patients and age- and exercise level-matched control subjects on an instrumented treadmill at self-selected treadmill walking speeds and at speeds representing +20% and -20% of the subjects' preferred speed. Surprisingly, no difference in preferred speed was observed between groups, possibly explained by an optimization of the mechanical cost of transport in both groups (the mechanical cost to travel a given distance; J/kg/m). The majority of limb kinematics and kinetics were also similar between groups, with the exception of greater ankle dorsiflexion angles during stance in CHF. Nevertheless, over two times greater ankle plantarflexion work during stance and per distance traveled is required for a given triceps surae muscle volume in CHF patients. This, together with a greater reliance on the ankle compared to the hip to power walking in CHF patients, especially at faster speeds, may contribute to the earlier onset of fatigue in CHF patients. This observation also helps explain the high correlation between triceps surae muscle volume and exercise capacity that has previously been reported in CHF. Considering the key role played by the plantarflexors in powering walking and their association with exercise capacity, our findings strongly suggest that exercise-based rehabilitation in CHF should not omit the ankle muscle group

The Interplay between Chemistry and Mechanics in the Transduction of a Mechanical Signal into a Biochemical Function

There are many processes in biology in which mechanical forces are generated. Force-bearing networks can transduce locally developed mechanical signals very extensively over different parts of the cell or tissues. In this article we conduct an overview of this kind of mechanical transduction, focusing in particular on the multiple layers of complexity displayed by the mechanisms that control and trigger the conversion of a mechanical signal into a biochemical function. Single molecule methodologies, through their capability to introduce the force in studies of biological processes in which mechanical stresses are developed, are unveiling subtle intertwining mechanisms between chemistry and mechanics and in particular are revealing how chemistry can control mechanics. The possibility that chemistry interplays with mechanics should be always considered in biochemical studies.Comment: 50 pages, 18 figure

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach