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Introduction Thyroid dysfunction is the most frequent endocrine immune related adverse event (irAE) in non-small cell lung cancer (NSCLC), typically arising 3–6 months into immune checkpoint inhibitor (ICI) therapy, but arising after ICI cessation, in some cases. Due to limited post-treatment adverse event reporting requirements on ICI trials, the incidence of ICI-induced thyroid dysfunction arising after therapy is unclear. We investigated ICI-induced thyroid dysfunction in a cohort of 294 NSCLC patients, with a specific focus on the post-treatment setting. Methods Retrospective analysis of ICI-induced thyroid dysfunction (clinically acted upon or laboratory only) was performed in 294 UCLA NSCLC patients treated 2012–2018. Clinically acted upon thyroid dysfunction was defined as thyroid diagnosis documentation and/or thyroid medication administration. Laboratory only dysfunction was defined as abnormal thyroid labs in the absence of clinical action. Timing of thyroid dysfunction relative to ICI treatment and thyroid monitoring patterns were also assessed. Results 82% (241/294) of ICI treated NSCLC patients had thyroid labs during treatment. Of these 241 patients, 13% (31/241) had clinically acted upon thyroid dysfunction prior to, 8% (18/241) during, and 4% (9/241) after ICI. Most patients, 66% (159/241), did not have thyroid labs after ICI, but in the 53 patients with labs and no prior clinical dysfunction, 17% (9/53) developed clinical dysfunction after ICI. In these 9 patients, median time from ICI initiation to dysfunction was 253 days. Two patients with post-treatment laboratory only dysfunction were observed. Conclusions ICI-induced thyroid dysfunction arising post-treatment appears more common than previously appreciated, warranting additional evaluation.

Background : Bicuspid aortic valve (BAV) is the most common congenital heart defect and is associated with a number of cardiac pathologies including coarctation of the aorta (CoA), aortic dilation, aortic stenosis, and premature coronary artery disease (CAD). Furthermore, BAV has been associated with left dominant coronary artery anatomy but there is still much debate regarding this association. To date, no study has investigated the association between coronary artery dominance and cardiac pathologies in patients with BAV. Methods : A total of 45 patients with BAV who underwent coronary computed tomography angiography (CTA) and/or cardiac catheterization at a single center were included. Coronary artery dominance, presence of CAD, CoA, and aortic dilation was determined from coronary CTA and/or cardiac catheterization reports. Incidence of aortic valve stenosis and aortic valve regurgitation was determined from echo reports. Results : Of the 45 patients with BAV, 80% (36) had right dominant coronary artery circulations. Patients with BAV with left dominant circulations had a significantly (p=0.04) higher incidence of CoA compared to patients with right dominant circulations (44% vs 14%). There was no significant difference when comparing the incidences of aortic dilation, aortic valve stenosis, aortic valve regurgitation and CAD in right and left dominant patients. Conclusions : Our study found a predominance of right dominant coronary artery circulation in patients with BAV, similar to the general population. Interestingly, left dominance was significantly associated with CoA in patients with BAV. This observation highlights the importance of further studies regarding how coronary artery dominance can be associated with other cardiovascular pathologies in patients with BAV.

The basal transcription factor TFE enhances transcription initiation by catalysing DNA strand-separation, a process that varies with temperature and ionic strength. Canonical TFE forms a heterodimeric complex whose integrity and function critically relies on a cubane iron-sulphur cluster residing in the TFEβ subunit. Halophilic archaea such as Haloferax volcanii have highly divergent putative TFEβ homologues with unknown properties. Here, we demonstrate that Haloferax TFEβ lacks the prototypical iron-sulphur cluster yet still forms a stable complex with TFEα. A second metal cluster contained in the zinc ribbon domain in TFEα is highly degenerate but retains low binding affinity for zinc, which contributes to protein folding and stability. The deletion of the tfeB gene in H. volcanii results in the aberrant expression of approximately one third of all genes, consistent with its function as a basal transcription initiation factor. Interestingly, tfeB deletion particularly affects foreign genes including a prophage region. Our results reveal the loss of metal centres in Hvo transcription factors, and confirm the dual function of TFE as basal factor and regulator of transcription.