Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Christian Spirituality and Social Transformation

The word “spirituality” has become increasingly common. What does it mean? It is not limited to spiritual practices, such as meditation, but suggests the pursuit of a life shaped by a sense of meaning, values, and perhaps transcendence. Although the word is used in different religions, and by people with no religious beliefs, its origins were Christian and referred to living life under the influence of God’s spirit. Nowadays, in a consciously plural world, Christian spirituality has a specific content whose origins are the Jewish and Christian scriptures. In particular, Christian spirituality is associated with following the teachings of Jesus Christ or imitating his values. The main New Testament word for this is “discipleship,” which has two main elements. First, there is a call to personal transformation (conversion). Second, Christians are to continue the mission of Jesus to transform the world and to build the kingdom of a God of love. In that fundamental sense, Christian spirituality is inherently concerned with social transformation. In the Gospel of Matthew, this includes sharing in Jesus’ work of forgiveness and healing. In the Gospel of Mark it involves selfless service of others. The history of Christian spirituality is a varied story of ways of approaching discipleship. Needless to say, part of what makes Christian spirituality distinctive is its underlying beliefs—in other words, how it understands the reality of God, the value of the material world, human nature, and identity and how these interconnect. The great variety of spiritual traditions and writings within Christianity originated at different times and places. However, they are continually being adapted in the light of new historical and cultural contexts. Scholars have sometimes found it helpful to identify different types of Christian spirituality. Their choices vary, and the types are interpretative tools rather than straightforward descriptions. “Types” help us to identify distinctive styles of spiritual wisdom. The ascetical type, sometimes associated with monasticism, highlights discipline and detachment from material pleasures as the pathway to spiritual growth. The mystical type focuses on the desire for an immediacy of presence to, and intuitive knowledge of, God, frequently via contemplative practice. The active type promotes everyday life and service to other people as the context for spiritual growth. The aesthetic type covers a range of ways in which the spiritual journey is expressed in and shaped by the arts, music, and literature. Finally the prophetic type of spirituality embraces an explicit commitment to social justice and the transformation of society. Christian spirituality has become a major area of study. It is an interdisciplinary field shaped by scripture, theology, and Christian history, but which may also draw upon psychology, the social sciences, literature, and the sciences. The study of Christian spirituality is also “self-implicating,” in the sense that it is not treated in a purely theoretical way but includes a quest for practical wisdom. Finally, the traditions of Christian spirituality increasingly engage with important issues of social and cultural transformation, for example interreligious dialogue, peace and reconciliation, ecological questions, the future of cities, the world of business, and the meaning of healthcare.</p

Illumination without Knowledge: Michel de Certeau's The Mystical Fable

The question whether or not God can be known or defined is central to Christian mysticism. On this topic, the writings on mysticism by the French Catholic priest and Jesuit, Michel de Certeau (1925-1986) are especially relevant and challenging. De Certeau was one of the most creative interdisciplinary thinkers of the late twentieth century as well as a highly original writer in reference to Christian mysticism. At the same time, de Certeau is particularly difficult to summarise or to interpret definitively. To begin with, he approached every subject from a transdisciplinary standpoint, drawing extensively upon history, theology, spirituality, cultural theory, politics, philosophy, psychoanalysis and the social sciences. De Certeau’s deliberately enigmatic style was also based on his underlying approach to epistemology – that is, to the nature of knowledge, its scope and its origins. Overall, de Certeau rejected what he saw as the dangers of philosophical fundamentalism that he detected in some aspects of European post-Enlightenment thought, notably a tendency towards rationalist positivism. Thus de Certeau questioned both the extent to which anything can really be fully known and also whether “knowledge” is reducible merely to a mental capacity to think logically or to make rational deductions about reality. Clearly this standpoint is particularly relevant to the question of whether, to what extent and how an ultimately mysterious God may be “known” or defined and plays a central role in his late, unfinished work on Christian mysticism, The Mystic Fable. </jats:p