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Background In post-coronavirus disease-19 (post-COVID-19) conditions (long COVID), systemic vascular dysfunction is implicated, but the mechanisms are uncertain, and the treatment is imprecise. Methods and results Patients convalescing after hospitalization for COVID-19 and risk factor matched controls underwent multisystem phenotyping using blood biomarkers, cardiorenal and pulmonary imaging, and gluteal subcutaneous biopsy (NCT04403607). Small resistance arteries were isolated and examined using wire myography, histopathology, immunohistochemistry, and spatial transcriptomics. Endothelium-independent (sodium nitroprusside) and -dependent (acetylcholine) vasorelaxation and vasoconstriction to the thromboxane A2 receptor agonist, U46619, and endothelin-1 (ET-1) in the presence or absence of a RhoA/Rho-kinase inhibitor (fasudil), were investigated. Thirty-seven patients, including 27 (mean age 57 years, 48% women, 41% cardiovascular disease) 3 months post-COVID-19 and 10 controls (mean age 57 years, 20% women, 30% cardiovascular disease), were included. Compared with control responses, U46619-induced constriction was increased (P = 0.002) and endothelium-independent vasorelaxation was reduced in arteries from COVID-19 patients (P Conclusion Patients with post-COVID-19 conditions have enhanced vascular fibrosis and myosin light change phosphorylation. Rho-kinase activation represents a novel therapeutic target for clinical trials.

Funder: Barts and the London Charity project (no. MGU0360) Senior Investigator award no. NF-SI-0512-10052, Funder: NIHR Cambridge BRC (no. IS-BRC-1215-20014), Funder: NIHR Biomedical Research Centre at Barts and The London School of Medicine and Dentistry, Funder: National Medical Research Council and BRC of Singapore, Funder: NIHR Birmingham Biomedical Research Centre (grant reference number BRC-1215-20009) European Union’s Horizon 2020 Research Innovation Program under grant agreement no. 633983 (ENSAT-HT), Funder: Barts and The London Charity, Funder: Barts and the London Charity project (no. MGU0360), Funder: Barts and the London Charity project, Primary aldosteronism (PA) due to a unilateral aldosterone-producing adenoma is a common cause of hypertension. This can be cured, or greatly improved, by adrenal surgery. However, the invasive nature of the standard pre-surgical investigation contributes to fewer than 1% of patients with PA being offered the chance of a cure. The primary objective of our prospective study of 143 patients with PA ( NCT02945904 ) was to compare the accuracy of a non-invasive test, [11C]metomidate positron emission tomography computed tomography (MTO) scanning, with adrenal vein sampling (AVS) in predicting the biochemical remission of PA and the resolution of hypertension after surgery. A total of 128 patients reached 6- to 9-month follow-up, with 78 (61%) treated surgically and 50 (39%) managed medically. Of the 78 patients receiving surgery, 77 achieved one or more PA surgical outcome criterion for success. The accuracies of MTO at predicting biochemical and clinical success following adrenalectomy were, respectively, 72.7 and 65.4%. For AVS, the accuracies were 63.6 and 61.5%. MTO was not significantly superior, but the differences of 9.1% (95% confidence interval = -6.5 to 24.1%) and 3.8% (95% confidence interval = -11.9 to 9.4) lay within the pre-specified -17% margin for non-inferiority (P = 0.00055 and P = 0.0077, respectively). Of 24 serious adverse events, none was considered related to either investigation and 22 were fully resolved. MTO enables non-invasive diagnosis of unilateral PA.

BackgroundWe investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals.Methods and resultsOne hundred and sixty-eight patients were evaluated 28–60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers. Compared with non-healthcare workers, healthcare workers were of similar age (51.3 (8.7) years vs 55.0 (12.4) years; p=0.09) more often women (26 (72%) vs 48 (38%); pIn adjusted multivariate logistic regression analysis, healthcare worker status associated with a binary classification (probable/very likely vs not present/unlikely) of adjudicated myocarditis (OR: 2.99; 95% CI (1.01 to 8.89) by 28–60 days postdischarge).After a mean (SD, range) duration of follow-up after hospital discharge of 450 (88) days (range 290, 627 days), fewer healthcare workers died or were rehospitalised (1 (3%) vs 22 (17%); p=0.038) and secondary care referrals for post-COVID-19 syndrome were common (42%) and similar to non-healthcare workers (38%; p=0.934).ConclusionHealthcare worker status was independently associated with the likelihood of adjudicated myocarditis, despite better antecedent health. Two in five healthcare workers had a secondary care referral for post-COVID-19 syndrome.Trial registration numberNCT04403607.

Primary aldosteronism (PA) due to a unilateral aldosterone-producing adenoma (APA) is a common, curable cause of hypertension, but invasive methods of diagnosis and treatment contribute to -17%, the pre-specified margin of non-inferiority. The best univariate predictors of complete clinical cure were home systolic blood pressure (SBP)

Background: The pathophysiology and trajectory of multiorgan involvement in post-COVID-19 syndrome is uncertain. Methods: A prospective, multicenter, longitudinal, cohort study involving post-COVID-19 patients enrolled in-hospital or early post-discharge (visit 1) and re-evaluated 28-60 days post-discharge (visit 2). Multisystem investigations included chest computed tomography with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging, digital electrocardiography, and multisystem biomarkers. The primary outcome was the adjudicated likelihood of myocarditis.Results: 161 patients (mean age 55 years, 43% female) and 27 controls with similar age, sex, ethnicity, and vascular risk factors were enrolled from 22 May 2020 to 2 July 2021 and had a primary outcome evaluation. Compared to controls, at 28-60 days post-discharge, patients with COVID-19 had persisting evidence of cardio-renal involvement, systemic inflammation, and hemostasis pathway activation. Myocarditis was adjudicated as being not likely (n=17; 10%), unlikely (n=56; 35%), probable (n=67; 42%) or very likely (n=21; 13%). Acute kidney injury (odds ratio, 95% confidence interval: 3.40 (1.13, 11.84); p=0.038) and low hemoglobin A1c (0.26 (0.07, 0.87); p=0.035) were multivariable associates of adjudicated myocarditis. During convalescence, compared to controls, COVID-19 was associated with worse health-related quality of life (EQ5D-5L) (pConclusions: The illness trajectory of COVID-19 includes persisting cardio-renal inflammation, lung damage and hemostasis activation. Adjudicated myocarditis occurred in one in eight hospitalized patients and was associated with impairments in health status, physical and psychological wellbeing during community convalescence. Public registration: ClinicalTrials.gov identifier is NCT04403607.

Aim: Quantitative comparison of the effects of intensive (IPT) or conventional (CPT) periodontal treatment on arterial blood pressure, endothelial function and inflammatory/metabolic biomarkers. Materials and methods: A systematic search was conducted to identify randomized controlled trials (RCT) of IPT (supra and subgingival instrumentation). Eight RCTs were included in the meta-analysis. Difference in change of systolic blood pressure (SBP) and diastolic blood pressure (DBP) before and after IPT or CPT were the primary outcomes. The secondary outcomes included: endothelial function and selected inflammatory/anti-inflammatory (CRP, IL-6, IL-10, IFN-γ) and metabolic biomarkers (HDL, LDL, TGs). Results: The overall effect estimates (pooled Weighted Mean Difference (WMD)) of the primary outcome for SBP and DBP was −4.3 mmHg [95%CI: −9.10–0.48], p = 0.08 and −3.16 mmHg [95%CI: −6.51–0.19], p = 0.06 respectively. These studies were characterized by high heterogeneity. Therefore, random effects model for meta-analysis was performed. Sub-group analyses confirmed statistically significant reduction in SBP [WMD = −11.41 mmHg (95%CI: −13.66, −9.15) P < 0.00001] and DBP [WMD = −8.43 mmHg (95%CI: −10.96,−5.91)P < 0.00001] after IPT vs CPT among prehypertensive/hypertensive patients, while this was not observed in normotensive individuals. The meta-analyses showed significant reductions in CRP and improvement of endothelial function following IPT at all analysed timepoints. Conclusions: IPT leads to improvement of the cardiovascular health in hypertensive and prehypertensive individuals.

Aim To investigate whether appetite-related hormones were predictors of weight regain in the Diabetes Remission Clinical Trial (DiRECT). Materials and methods DiRECT is a cluster-randomized clinical trial, designed to assess the effect of weight loss on type 2 diabetes remission. For this post hoc analysis, data were available for 253 (147 interventions, 106 controls) individuals with type 2 diabetes (age 53.6 ± 7.5 years, body mass index 34.7 ± 4.4 kg/m2 , 59% men). Intervention participants received a 24-month weight management programme, and controls remained on usual diabetes care. Fasting plasma concentrations of leptin, ghrelin, glucagon-like peptide-1 and peptide YY were measured at baseline, 12 months and 24 months in all participants, and at 5 months in a subset of participants in the intervention (n = 56) and control groups (n = 22). Potential predictors were examined using multivariable linear regression models. Results The intervention group lost 14.3 ± 6.0% body weight at 5 months but regained weight over time, with weight losses of 10.0 ± 7.5% at 12 months and 7.6 ± 6.3% at 24 months. Weight loss in controls was 1.1 ± 3.7% and 2.1 ± 5.0% at 12 and 24 months, respectively. Body weight increased by 2.3% (95% confidence interval [CI] 0.4, 4.1; P = 0.019) between 12 and 24 months for every 1-ng/mL increase in ghrelin between baseline and 12 months, and weight regain between 12 and 24 months was increased by 1.1% (95% CI 0.2, 2.0; P = 0.023) body weight for every 1-ng/mL increase in ghrelin at 12 months. Conclusion The rise in ghrelin (but not any other measured hormone) during diet-induced weight loss was a predictor of weight regain during follow-up, and concentrations remained elevated over time, suggesting a small but significant compensatory drive to regain weight. Attenuating the effects of ghrelin may improve weight-loss maintenance.

ObjectivesTo investigate psychotropic prescribing in the intellectual disabilities population over 10 years, and associated mental ill health diagnoses.DesignComparison of cross-sectional data in 2002–2004 (T1) and 2014 (T2). Longitudinal cohort study with detailed health assessments at T1 and record linkage to T2 prescribing data.SettingGeneral community.Participants1190 adults with intellectual disabilities in T1 compared with 3906 adults with intellectual disabilities in T2. 545/1190 adults with intellectual disabilities in T1 were alive and their records linked to T2 prescribing data.Main outcome measuresEncashed regular and as-required psychotropic prescriptions.Results50.7% (603/1190) of adults in T1 and 48.2% (1881/3906) in T2 were prescribed at least one psychotropic; antipsychotics: 24.5% (292/1190) in T1 and 16.7% (653/3906) in T2; antidepressants: 11.2% (133/1190) in T1 and 19.1% (746/3906) in T2. 21.2% (62/292) prescribed antipsychotics in T1 had psychosis or bipolar disorder, 33.2% (97/292) had no mental ill health or problem behaviours, 20.6% (60/292) had problem behaviours but no psychosis or bipolar disorder. Psychotropics increased from 47.0% (256/545) in T1 to 57.8% (315/545) in T2 (pConclusionsDespite concerns about antipsychotic prescribing and guidelines recommending their withdrawal, it appears that while fewer antipsychotic prescriptions were initiated by T2 than in T1, people were not withdrawn from them once commenced. People with problem behaviours had increased prescribing. There was also a striking increase in antidepressant prescriptions. Adults with intellectual disabilities need frequent and careful medication reviews.

Primary aldosteronism (PA) is now considered the sole, often curable, cause of hypertension in 5-10% of patients. Yet there has been only one RCT, and practice has changed little since the advent of CT scanning. Adrenal vein sampling (AVS) and adrenalectomy remain the standard, invasive interventions, leading to a 50% reduction in pill count as the average clinical improvement. Study Design In MATCH (Is Metomidate PET-CT superior to Adrenal vein sampling in predicting ouTCome from adrenalectomy in patients with primary Hyperaldosteronism), 142 patients, mean age 52, 32% female, 32% of African ancestry, 46% hypokalemic, had both AVS and 11C-metomidate PET CT (MTO) in random order, and were referred for surgery if aldosterone/cortisol ratio differed >4-fold between adequately cannulated adrenal veins, and/or SUVmax on MTO was >1.25 higher, in a definite tumour, than the opposite adrenal. The primary outcome is the proportion of patients in whom adrenalectomy achieved complete or partial biochemical or clinical cure, analysed hierarchically using PASO criteria.1 Anticipating ~50% incidence of unilateral PA, MATCH is powered to detect 25% superiority of MTO vs AVS, or non-inferiority at a lower-bound CI of -17%. Secondary outcomes include non-randomised comparison of outcomes between unilateral and bilateral PA; prediction of clinical outcome from the home BP (12 readings over 3 days) before and after starting spironolactone 100 mg od for 4 weeks; quality-of-life assessments; and analyses, by RNAseq, of genotype and transcriptomes of 56 of the CYP11B2-positive tumors, correlated with ethnicity and outcomes. Results: The analysis set is 75 patients who, on 31 Dec 2020, had undergone adrenalectomy with > 6 months follow-up. 67 patients (89%) had complete biochemical cure following PASO criteria,1 and 63 (84%) had complete or partial clinical cure. In 39 of the surgical patients, only one of MTO or AVS was scored as high-probability using criteria above. This score was confirmed at the multi-centre, Multi-Disciplinary Team (MDT) meeting which reviewed all MTO scans without knowledge of AVS. In the primary analysis, comparing accuracy of MTO and AVS by McNemar test, the 39 discordant results were allocated as a win to the positive investigation, if the patient was cured, or to the negative investigation, if not cured. 50/56 CYP11B2-positive tumors had a known mutation; the frequency was CACNA1D>KCNJ5>ATP1A1>ATP2B3>CTNNB1>GNAQ>CLCN2, differing between patients whose hypertension was completely or partially cured. Two other tumors had novel gene mutations. Several RNAseq transcripts varied with genotype and outcome, including some encoding measurable, secreted proteins. Full primary and secondary outcomes will be presented. 1. Williams TA, et al. Lancet Diabetes Endocrinol. 2017;5:689-699