Hypothyroidism and the risk of lower extremity arterial disease

Background: Although an independent association between hypothyroidism and coronary artery disease has been demonstrated, few studies have examined the association between hypo-thyroidism and peripheral arterial disease. In the current study, we test the hypothesis that there is an independent association between hypothyroidism and lower extremity arterial disease. Methods: We retrospectively compared the prevalence of hypothyroidism in patients who had infra-inguinal arterial bypass surgery over a 6-year period with that of a control group of surgical patients who had pure cardiac valve surgery during the same time period. Both unadjusted and adjusted odds ratios were calculated to estimate the association between hypothyroidism and lower extremity arterial disease. Results: A total of 614 cases and 529 control subjects had surgery during the study period. When comparing all subjects, there was no association between hypothyroidism and lower extremity arterial disease (unadjusted odds ratio 0.88; 95% confidence intervals [CI]: 0.61-1.28). However, gender was found to be a significant effect modifier (P \u3c 0.001), and gender-stratified analyses were subsequently performed. In men, there was a positive independent association between hypothyroidism and lower extremity arterial disease (adjusted odds ratio 2.65; 95% CI: 1.19-5.89), whereas in women there was a negative independent association (adjusted odds ratio 0.22; 95% CI: 0.11-0.46). Conclusions: Gender is a significant effect modifier for the association between hypothyroidism and lower extremity arterial disease. The association is positive in men and negative in women. Future prospective studies that evaluate hypothyroidism as a risk factor for peripheral arterial disease should consider gender stratification in order to corroborate this finding. © 2010 Mazzeffi et al, publisher and licensee Dove Medical Press Ltd

Case Report Asystole after Orthotopic Lung Transplantation: Examining the Interaction of Cardiac Denervation and Dexmedetomidine

Dexmedetomidine is an α 2 -receptor agonist commonly used for sedation and analgesia in ICU patients. Dexmedetomidine is known to provide sympatholysis and also to have direct atrioventricular and sinoatrial node inhibitory effects. In rare instances, orthotopic lung transplantation has been associated with disruption of autonomic innervation of the heart. The combination of this autonomic disruption and dexmedetomidine may be associated with severe bradycardia and/or asystole. Since orthotopic lung transplant patients with parasympathetic denervation will not respond with increased heart rate to anticholinergic therapy, bradyarrhythmias must be recognized and promptly treated with direct acting beta agonists to avoid asystolic cardiac events

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

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

“Socratism as a Vocation.”

This paper discusses the rhetorical problems teachers face in presenting Socratic activity to students, and it then argues that parallel problems arise in presenting liberal education to many academic colleagues. Given the nature of philosophy and the nature of expertise in today’s academy, most academics will not understand, and perhaps be hostile to, philosophy, and philosophers may sometimes seem to them both arrogant and ignorant. The contemporary academy, dominated by assumptions Weber articulates in "Science as a Vocation," does not make room for philosophical activity and practitioners of philosophy in the classroom (in various departments) must adopt rhetorically appropriate postures in order to create safe spaces for Socratic activity