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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.

OBJECTIVE: The study objective was to determine what proportion of asymptomatic patients had resectable lung cancer detected through lung cancer screening versus incidentally. METHODS: We performed a retrospective study of patients who underwent resection for lung cancer between January 2015 and December 2020. We then assessed whether asymptomatic patients with incidentally found lung cancers were eligible for lung cancer screening using the National Comprehensive Cancer Network, United States Preventive Services Task Force, Centers for Medicare & Medicaid Services, American College of Chest Physicians, American Cancer Society, and American Society of Clinical Oncology guidelines. RESULTS: Of 539 patients who underwent resection for primary lung cancer, 437 (81%) were asymptomatic and 355 (66%) of these patients had lung cancer found discovered incidentally. Of the 355 patients with incidentally detected lung cancer, 10 were excluded for insufficient data. Of the remaining 345 patients, 110 (32%) would have been eligible for screening using National Comprehensive Cancer Network guidelines, 65 (19%) using 2021 United States Preventive Services Task Force guidelines, 53 (15%) using 2013 United States Preventive Services Task Force guidelines, 64 (19%) using 2022 Centers for Medicare & Medicaid Services guidelines, 52 (15%) using 2015 Centers for Medicare & Medicaid Services/American College of Chest Physicians guidelines, and 45 (13%) using American Cancer Society/American Society of Clinical Oncology guidelines. Of the 280 patients who were screen ineligible by 2021 United States Preventive Services Task Force criteria, 143 patients (51%) never smoked, 112 patients (40%) quit smoking more than 15 years ago, 89 patients (32%) did not smoke at least 20 pack-years, and 44 patients (16%) were ineligible due to age. CONCLUSIONS: The majority of asymptomatic patients with resectable lung cancers had lung cancer identified incidentally and not through lung cancer screening. Most of these patients were not eligible for screening under current guidelines. This study suggests a need for improved lung cancer screening implementation and further investigation in the identification and assessment of risk factors for lung cancer.

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.

Background Early appropriate antibiotic selection is life saving in sepsis. Facility-level antibiograms inform antibiotic selection after pathogen identification and before susceptibility results are available, but only if ≥ 30 isolates from a given species are tested in the prior year. Stenotrophomonas maltophilia (SM) has a complex resistance profile and is associated with an 8-fold mortality increase. We hypothesized that a regional antibiogram may help inform clinical decision-making for severe SM infections. Methods To generate a regional SM antibiogram, we conducted a cross-sectional, voluntary survey of 2015 cumulative facility-level antibiograms from all hospitals in LA county. Non-respondents were contacted to improve response rates. Isolates from sterile sources were pooled. Susceptibility was aggregated and percent susceptible was calculated only when all isolates were tested, i.e. not reflex testing. To identify optimal combination empiric therapy for SM infections, we generated a combination antibiogram using broth microdilution results from a single tertiary care facility in LA. Results Antibiograms were submitted by 85/100 (85%); 50 hospitals (59%) reported SM (n = 1719 isolates, Table 1). Hospitals commonly (25/50) reported data for