Heart Transplantation and Donation After Circulatory Death in Children. A Review of the Technological, Logistical and Ethical Framework

Copyright \ua9 2025 Kenny, Armstrong, Berman, Brierley, Crossland, Dark, Gardiner, Large, Manas, Nassar, Shaw and Simpson.Heart transplant for adults following Donation after Circulatory Death (DCD) is well established in many parts of the world, including the United Kingdom (UK). Small child DCD hearts have now been recovered in the UK and internationally utilising novel technologies. Despite these recent advances, extension of this practice to pediatric cardiac transplantation has been slow and difficult despite the severe shortage of donors for children leading to a high number of deaths annually of children waiting for heart transplant. This is in direct contrast with the thriving UK programme of adult DCD heart transplant and pediatric DCD donation for non-cardiac organs. There has been insufficient action in addressing this inequality thus far. Barriers to development of a pediatric cardiac DCD programme are multifaceted: ethical concerns, technological paucity, financial and logistical hurdles. We describe the background, live issues, current developments and how we are driving resources toward a sustainable DCD programme for small children in the UK to provide valuable insights to other countries of the elements and principles at play. This is a call to responsible bodies to take urgent and achievable actions to establish an equitable paediatric DCD cardiac programme for donors, recipients and their families

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Evaluation of Possible Effects of a Potassium Channel Modulator on Temporal Processing by Cochlear Implant Listeners

Temporal processing by cochlear implant listeners is degraded and is affected by auditory deprivation. The fast-acting Kv3.1 potassium channel is important for sustained temporally accurate firing and is also susceptible to deprivation, the effects of which can be partially restored in animals by the molecule AUT00063. We report the results of a randomised placebo-controlled double-blind study on psychophysical tests of the effects of AUT00063 on temporal processing by CI listeners. The study measured the upper limit of temporal pitch, gap detection, and discrimination of low rates (centred on 120 pps) for monopolar pulse trains presented to an apical electrode. The upper limit was measured using the optimally efficient midpoint comparison (MPC) pitch-ranking procedure; thresholds were obtained for the other two measures using an adaptive procedure. Twelve CI users (MedEl and Cochlear) were tested before and after two periods of AUT00063 or placebo in a within-subject crossover study. No significant differences occurred between post-drug and post-placebo conditions. This absence of effect occurred despite high test-retest reliability for all three measures, obtained by comparing performance on the two baseline visits, and despite the demonstrated sensitivity of the measures to modest changes in temporal processing obtained in other studies from our laboratory. Hence, we have no evidence that AUT00063 improves temporal processing for the doses and patient population employed

Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure

<p>Abstract</p> <p>Background -</p> <p>Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly and Thr164Ile were suggested to have an effect in heart failure. We evaluated these polymorphisms relative to clinical characteristics and prognosis of alarge cohort of patients with heart failure of different etiologies.</p> <p>Methods -</p> <p>We studied 501 patients with heart failure of different etiologies. Mean age was 58 years (standard deviation 14.4 years), 298 (60%) were men. Polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism.</p> <p>Results -</p> <p>During the mean follow-up of 12.6 months (standard deviation 10.3 months), 188 (38%) patients died. Distribution of genotypes of polymorphism Arg16Gly was different relative to body mass index (χ²= 9.797;p = 0.04). Overall the probability of survival was not significantly predicted by genotypes of Gln27Glu, Arg16Gly, or Thr164Ile. Allele and haplotype analysis also did not disclose any significant difference regarding mortality. Exploratory analysis through classification trees pointed towards a potential association between the Gln27Glu polymorphism and mortality in older individuals.</p> <p>Conclusion -</p> <p>In this study sample, we were not able to demonstrate an overall influence of polymorphisms Gln27Glu and Arg16Gly of beta-2 receptor gene on prognosis. Nevertheless, Gln27Glu polymorphism may have a potential predictive value in older individuals.</p

The history of falls and the association of the timed up and go test to falls and near-falls in older adults with hip osteoarthritis

Abstract Background Falling accounts for a significant number of hospital and long-term care admissions in older adults. Many adults with the combination of advancing age and functional decline associated with lower extremity osteoarthritis (OA), are at an even greater risk. The purpose of this study was to describe fall and near-fall history, location, circumstances and injuries from falls in a community-dwelling population of adults over aged 65 with hip OA and to determine the ability of the timed up and go test (TUG) to classify fallers and near-fallers. Method A retrospective observational study of 106 older men and women with hip pain for six months or longer, meeting a clinical criteria for the presence of hip OA at one or both hips. An interview for fall and near-fall history and administration of the TUG were administered on one occasion. Results Forty-five percent of the sample had at least one fall in the past year, seventy-seven percent reported occasional or frequent near-falls. The majority of falls occurred during ambulation and ascending or descending steps. Forty percent experienced an injury from the fall. The TUG was not associated with history of falls, but was associated with near-falls. Higher TUG scores occurred for those who were older, less mobile, and with greater number of co-morbidities. Conclusion A high percentage of older adults with hip OA experience falls and near-falls which may be attributed to gait impairments related to hip OA. The TUG could be a useful screening instrument to predict those who have frequent near-falls, and thus might be useful in predicting risk of future falls in this population.</p

Omics analysis of educated platelets in cancer and benign disease of the pancreas

Pancreatic ductal adenocarcinoma (PDAC) is traditionally associated with thrombocytosis/hypercoagulation and novel insights on platelet-PDAC “dangerous liaisons” are warranted. Here we performed an integrative omics study investigating the biological processes of mRNAs and expressed miRNAs, as well as proteins in PDAC blood platelets, using benign disease as a reference for inflammatory noise. Gene ontology mining revealed enrichment of RNA splicing, mRNA processing and translation initiation in miRNAs and proteins but depletion in RNA transcripts. Remarkably, correlation analyses revealed a negative regulation on SPARC transcription by isomiRs involved in cancer signaling, suggesting a specific ”education” in PDAC platelets. Platelets of benign patients were enriched for non-templated additions of G nucleotides (#ntaG) miRNAs, while PDAC presented length variation on 3′ (lv3p) as the most frequent modification on miRNAs. Additionally, we provided an actionable repertoire of PDAC and benign platelet-ome to be exploited for future studies. In conclusion, our data show that platelets change their biological repertoire in patients with PDAC, through dysregulation of miRNAs and splicing factors, supporting the presence of de novo protein machinery that can “educate” the platelet. These novel findings could be further exploited for innovative liquid biopsies platforms as well as possible therapeutic targets

Brown Adipose Tissue in Humans Is Activated by Elevated Plasma Catecholamines Levels and Is Inversely Related to Central Obesity

BACKGROUND: Recent studies have shown that adult human possess active brown adipose tissue (BAT), which might be important in controlling obesity. It is known that ß-adrenoceptor-UCP1 system regulates BAT in rodent, but its influence in adult humans remains to be shown. The present study is to determine whether BAT activity can be independently stimulated by elevated catecholamines levels in adult human, and whether it is associated with their adiposity. METHODOLOGY/PRINCIPAL FINDINGS: We studied 14 patients with pheochromocytoma and 14 normal subjects who had performed both ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and plasma total metanephrine (TMN) measurements during 2007-2010. The BAT detection rate and the mean BAT activity were significantly higher in patients with elevated TMN levels (Group A: 6/8 and 6.7±2.1 SUVmean· g/ml) than patients with normal TMN concentrations (Group B: 0/6 and 0.4±0.04 SUVmean· g/ml) and normal subjects (Group C: 0/14 and 0.4±0.03 SUVmean·g/ml). BAT activities were positively correlated with TMN levels (R = 0.83, p<0.0001) and were inversely related to body mass index (R = -0.47, p = 0.010), visceral fat areas (R = -0.39, p = 0.044), visceral/total fat areas (R = -0.52, p = 0.0043) and waist circumferences (R = -0.43, p = 0.019). Robust regression revealed that TMN (R = 0.81, p<0.0001) and waist circumferences (R = -0.009, p = 0.009) were the two independent predictors of BAT activities. CONCLUSIONS/SIGNIFICANCE: Brown adipose tissue activity in adult human can be activated by elevated plasma TMN levels, such as in the case of patients with pheochromocytoma, and is negatively associated with central adiposity

Heat shock proteins in stabilization of spontaneously restored sinus rhythm in permanent atrial fibrillation patients after mitral valve surgery

A spontaneously restored sinus rhythm in permanent atrial fibrillation patients has been often observed after mitral valve (MV) surgery, but persisting duration in sinus rhythm varies from patient to patient. Heat shock proteins (Hsps) may be involved in pathogenesis of atrial fibrillation. We hypothesized that stabilization of restored sinus rhythm is associated with expression of Hsps in the atria. To test this hypothesis, clinical data, biopsies of right atrial appendage, and blood samples were collected from 135 atrial fibrillation patients who spontaneously restored sinus rhythm after conventional isolated MV replacement. Comparison was made between patients who had recurrence of atrial fibrillation within 7 days (AF) vs. patients with persisted sinus rhythm for more than 7 days (SR). Results showed that SR patients had higher activity of heat shock transcription factor 1 (HSF1) as well as upregulated expressions of heat shock cognate 70, Hsp70, and Hsp27 in the tissues. The activation of HSF1–Hsps pathway was associated with less-aggressive pathogenesis as reflected by lower rates of myolysis, apoptosis, interstitial fibrosis, and inflammation in SR patients. However, Hsp60 was lower in both tissue and plasma in SR patients, and was positively correlated with apoptosis, interstitial fibrosis, and inflammation. These findings suggest that the Hsps play important roles in stabilization of restored sinus rhythm after MV surgery by inhibiting AF-related atrial remodeling and arrhythmogenic substrates in atrial fibrillation patients. Low circulating Hsp60 levels preoperatively might predict a stable spontaneously restored sinus rhythm postoperatively

An individually-tailored multifactorial intervention program for older fallers in a middle-income developing country: Malaysian Falls Assessment and Intevention Trial (MyFAIT)

Background: In line with a rapidly ageing global population, the rise in the frequency of falls will lead to increased healthcare and social care costs. This study will be one of the few randomized controlled trials evaluating a multifaceted falls intervention in a low-middle income, culturally-diverse older Asian community. The primary objective of our paper is to evaluate whether individually tailored multifactorial interventions will successfully reduce the number of falls among older adults. Methods: Three hundred community-dwelling older Malaysian adults with a history of (i) two or more falls, or (ii) one injurious fall in the past 12 months will be recruited. Baseline assessment will include cardiovascular, frailty, fracture risk, psychological factors, gait and balance, activities of daily living and visual assessments. Fallers will be randomized into 2 groups: to receive tailored multifactorial interventions (intervention group); or given lifestyle advice with continued conventional care (control group). Multifactorial interventions will target 6 specific risk factors. All participants will be re-assessed after 12 months. The primary outcome measure will be fall recurrence, measured with monthly falls diaries. Secondary outcomes include falls risk factors; and psychological measures including fear of falling, and quality of life.Previous studies evaluating multifactorial interventions in falls have reported variable outcomes. Given likely cultural, personal, lifestyle and health service differences in Asian countries, it is vital that individually-tailored multifaceted interventions are evaluated in an Asian population to determine applicability of these interventions in our setting. If successful, these approaches have the potential for widespread application in geriatric healthcare services, will reduce the projected escalation of falls and fall-related injuries, and improve the quality of life of our older community