Temporal evolution of chest radiographic appearances in COVID-19 with clinicoradiological associations: a multicentre United Kingdom resident-led study.

AIM: To describe the (a) frequency of improving, static, and worsening chest radiograph (CXR) appearances; (b) differences in demographic, initial rudimentary haematological and CXR variables and these patterns; and (c) frequency of different trajectories of serial CXR evolution, in COVID-19 patients presenting consecutively. MATERIALS AND METHODS: This multicentre retrospective study included all COVID-19 patients admitted from 1-30 April 2020, meeting the inclusion criteria across 24 (blinded) hospitals. Follow-up CXRs on admission, the subsequent (where available), and at 4-8 weeks were scored for the presence of parenchymal opacities across six zones. Three cohorts were defined: improved, static, and/or worsened. The chi-squared and Kruskal-Wallis tests were used to compare demographic, laboratory, and CXR variables. Trajectories of CXR evolution were assessed when all three CXRs were available (226 patients). RESULTS: Of 452 included patients (median age 66 years, interquartile range 54.3-79, 262 men), 211 (46.7%) improved, 140 (31%) were static, and 101 (22.3%) worsened. Improving patients were more likely younger, with a classic COVID-19 radiograph and higher initial CXR zonal severity scores (both p<0.001), while worsening patients had lower initial lymphocyte counts (p=0.008). The most frequent trajectory was worsened then improved (n=63, 27.9%) followed by static then improved (n=46, 20.4%) and static (n=42, 18.6%). CONCLUSION: Most patients with COVID-19 during the first wave of the pandemic demonstrated radiographic improvement; these patients were more likely younger with classic COVID-19 appearances and initially more extensive abnormality. Conversely, radiographic deterioration was associated with lower lymphocyte counts. The three most common trajectories were worsening then improvement, static then improvement, and static throughout.

Academic clinical fellows in radiology: how can we improve success?

AIM: To survey past and current radiology academic clinical fellows (ACFs) for feedback on their experiences, academic achievements, challenges faced in balancing academic and clinical responsibilities, and opinion on how to optimise the fellowship programme. MATERIALS & METHODS: A 26-question online survey approved by the Royal College of Radiologists (RCR) Academic Committee was distributed over a 7-month period (June 2021 to January 2022) to current and past radiology ACFs via the National Institute for Health and Care Research (NIHR) integrated academic training imaging leads, radiology training programme directors, and social media. RESULTS: Thirty-five survey responses were received from past or present ACFs. Of the respondents, 42.8% (15/35) entered ACF training from another research post, and most continued their academic interests after ACF training (59.3%, 16/27 that had completed the post). The majority (22/35, 63%) had or were in the process of obtaining a postgraduate research degree. The most common academic outputs were scientific publications and national/international conference presentations. Most (23/35, 66%) would recommend the ACF post to colleagues, although some found it challenging balancing on-call and examination commitments during training. CONCLUSIONS: Entry into the radiology ACF programme is often after a prior academic post. Many ACFs appear to enjoy their fellowship experience and continue academic interests after training, some achieving higher research degrees. Challenges in balancing clinical workload require some flexibility from local clinical and academic supervisors. Suggestions for alternative structuring of the ACF pathway and how to optimise entry into these competitive posts are also outlined.

The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders.

Ketamine is a non-competitive antagonist at the N-methyl-d-aspartate receptor. It has recently been found to have antidepressant effects and is a drug of abuse, suggesting it may have dopaminergic effects. To examine the effect of ketamine on the dopamine systems, we carried out a systematic review and meta-analysis of dopamine measures in the rodent, human and primate brain following acute and chronic ketamine administration relative to a drug-free baseline or control condition. Systematic search of PubMed and PsychInfo electronic databases yielded 40 original peer-reviewed studies. There were sufficient rodent studies of the acute effects of ketamine at sub-anaesthetic doses for meta-analysis. Acute ketamine administration in rodents is associated with significantly increased dopamine levels in the cortex (Hedge's g= 1.33, P<0.01), striatum (Hedge's g=0.57, P<0.05) and the nucleus accumbens (Hedge's g=1.30, P<0.05) compared to control conditions, and 62-180% increases in dopamine neuron population activity. Sub-analysis indicated elevations were more marked in in vivo (g=1.93) than ex vivo (g=0.50) studies. There were not enough studies for meta-analysis in other brain regions studied (hippocampus, ventral pallidum and cerebellum), or of the effects of chronic ketamine administration, although consistent increases in cortical dopamine levels (from 88 to 180%) were reported in the latter studies. In contrast, no study showed an effect of anaesthetic doses (>100 mg kg-1) of ketamine on dopamine levels ex vivo, although this remains to be tested in vivo. Findings in non-human primates and in human studies using positron emission tomography were not consistent. The studies reviewed here provide evidence that acute ketamine administration leads to dopamine release in the rodent brain. We discuss the inter-species variation in the ketamine induced dopamine release as well as the implications for understanding psychiatric disorders, in particular substance abuse, schizophrenia, and the potential antidepressant properties of ketamine, and comparisons with stimulants and other NMDA antagonists. Finally we identify future research needs.

The dopamine hypothesis of bipolar affective disorder: the state of the art and implications for treatment.

Bipolar affective disorder is a common neuropsychiatric disorder. Although its neurobiological underpinnings are incompletely understood, the dopamine hypothesis has been a key theory of the pathophysiology of both manic and depressive phases of the illness for over four decades. The increased use of antidopaminergics in the treatment of this disorder and new in vivo neuroimaging and post-mortem studies makes it timely to review this theory. To do this, we conducted a systematic search for post-mortem, pharmacological, functional magnetic resonance and molecular imaging studies of dopamine function in bipolar disorder. Converging findings from pharmacological and imaging studies support the hypothesis that a state of hyperdopaminergia, specifically elevations in D2/3 receptor availability and a hyperactive reward processing network, underlies mania. In bipolar depression imaging studies show increased dopamine transporter levels, but changes in other aspects of dopaminergic function are inconsistent. Puzzlingly, pharmacological evidence shows that both dopamine agonists and antidopaminergics can improve bipolar depressive symptoms and perhaps actions at other receptors may reconcile these findings. Tentatively, this evidence suggests a model where an elevation in striatal D2/3 receptor availability would lead to increased dopaminergic neurotransmission and mania, whilst increased striatal dopamine transporter (DAT) levels would lead to reduced dopaminergic function and depression. Thus, it can be speculated that a failure of dopamine receptor and transporter homoeostasis might underlie the pathophysiology of this disorder. The limitations of this model include its reliance on pharmacological evidence, as these studies could potentially affect other monoamines, and the scarcity of imaging evidence on dopaminergic function. This model, if confirmed, has implications for developing new treatment strategies such as reducing the dopamine synthesis and/or release in mania and DAT blockade in bipolar depression.