Faculty Bibliography

Coccidioidomycosis rarely presents as a lung mass, hypereosinophilia, and disseminated pericarditis with pericardial effusion. Even rarer is a case that presents with the constellation of all these findings. We present a case of coccidioidomycosis in an immunocompetent young Jamaican male with all these features, set against an interesting epidemiological context of a likely exposure to coccidioidomycosis spores during an on-foot crossing of the Mexican border into Texas. His treatment course was complicated by declining liver and kidney function due to triazole antifungal therapy, necessitating titration of these doses to tolerable levels. This case highlights the importance of a detailed travel history in unraveling infectious disease diagnoses and underscores the need for high clinical suspicion for coccidioidomycosis, even in patients outside of known endemic regions.

Medical treatment of Cushing syndrome (CS) with steroidogenesis inhibitors or ACTH-directed agents is typically given using a titration strategy to achieve "normal" exposure to cortisol, as determined by a 24-hour urine free cortisol (UFC) measurement. This approach generally achieves similar serum cortisol levels across the day and fails to provide a normal diurnal pattern of cortisol. Chronotherapy addresses this problem through weighted afternoon/evening dosing of cortisol-lowering drugs. Additionally, because of day-to-day variability of cortisol production, patients may be undertreated on days of higher cortisol production and overtreated on days of lower cortisol production. A "block and replace" strategy is an alternative approach in which consistent biochemical glucocorticoid deficiency is the goal, with added glucocorticoid replacement to provide physiologic diurnal exposure to cortisol. Recently, the term mild autonomous cortisol secretion (MACS) has been used to describe patients without clinical features of CS who fail to suppress cortisol after 1 mg dexamethasone. MACS includes individuals with an adrenal mass(es) who may have hypertension, type 2 diabetes mellitus, and/or osteoporosis. The role of medical vs surgical treatment of MACS is currently debated. We here review the advantages and disadvantages of each approach to medical treatment of CS and MACS, concluding that "block and replace" deserves wider consideration, especially in patients who have severe disease, and to avoid adrenal insufficiency in those with highly variable UFC, or are taking agents that may cause adrenal insufficiency. Conversely, in those with mild disease, chronotherapy normalizes nighttime cortisol exposure while reducing drug burden.

CONTEXT/UNASSIGNED:Although menstrual dysfunction occurs in Cushing syndrome (CS), drivers of its prevalence and prognosis are poorly documented. OBJECTIVE/UNASSIGNED:Assess the prevalence of menstrual dysfunction, time to resolution after restoration of eucortisolism, and predictive factors for development and resolution. DESIGN/UNASSIGNED:Retrospective evaluation. SETTING/UNASSIGNED:Tertiary referral center. PATIENTS/UNASSIGNED:93 women treated for CS from 1987 to 2024. INTERVENTIONS/UNASSIGNED:Surgery, medical therapy, and/or irradiation to restore eucortisolism. MAIN OUTCOME MEASURES/UNASSIGNED:Prevalence of affected menses; rate and time to return to baseline pattern after remission. Patient, hormonal, tumor, and treatment factors predicting resolution. RESULTS/UNASSIGNED:< .0001) predicted a delayed (>6 months) return to baseline. CONCLUSION/UNASSIGNED:Two-thirds of women with CS have menstrual dysfunction due to cortisol-induced suppression of gonadotropins. In most women with minimal pituitary damage, menses return to baseline after a median of 6 months of eucortisolism. Significant overweight can delay resolution.

OBJECTIVE:The desmopressin stimulation test (DesST) is used to identify Cushing disease (CD). Reportedly, most healthy people and patients with non-neoplastic hypercortisolism lack a significant response. We aimed to evaluate and improve DesST specificity (Sp). DESIGN/METHODS:Prospective evaluation of four DesST protocols in healthy volunteers. METHODS:Twenty healthy volunteers underwent four DesST protocols in a randomized order. Protocols involved fluid restriction with desmopressin 10 µg (10NPO; 'standard'), 4 µg (4NPO), and 10 µg preceded by dexamethasone 1 mg (10+DexNPO); and desmopressin 10 µg without fluid restriction (10H2O). We evaluated Sp for each protocol, using established response criteria. RESULTS:Previous criteria of relative increases of 35% and/or 20% for ACTH and cortisol, respectively, had low Sp: 50% (95% CI: 28-72%; 10NPO) to 85% (95% CI: 69-100%; 10+DexNPO). Using absolute ACTH increase >8.1 pmol/L (37 pg/mL) improved Sp to 100% across all protocols. Compared with 10NPO, median ACTH and cortisol were lower throughout during 10+DexNPO and also at +15 min during 4NPO (ACTH: 4.4 vs 4.9 pmol/L (19.9 vs 22.1 pg/mL), P = 0.06; cortisol: 248 vs 284 nmol/L (9.0 vs 10.3 µg/dL), P = 0.01). 10H2O and 10NPO results were similar. Adverse events were mild; hyponatremia occurred after 5/80 tests. CONCLUSION/CONCLUSIONS:After desmopressin, healthy volunteers have small absolute increases in ACTH and cortisol that equate to large relative changes from baseline. Optimized response criteria should likely incorporate absolute values. Fluid restriction did not impact Sp, but using a lower desmopressin dose and dexamethasone pre-treatment are promising ways to improve diagnostic accuracy, if sensitivity is maintained in CD. SIGNIFICANCE STATEMENT/CONCLUSIONS:Half of healthy volunteers had a response consistent with Cushing disease (CD) during a commonly used 10 µg desmopressin stimulation test, interpreted using relative ACTH and/or cortisol increases. This puts the test's reliability for excluding CD in question, particularly in settings of mild hypercortisolism. These situations include differentiating CD from non-neoplastic hypercortisolism, identifying cyclic ectopic ACTH-producing tumors during nadir phases, and establishing early CD recurrence. Optimized response criteria likely require absolute ACTH and/or cortisol cutoffs. Using a reduced 4 µg dose of desmopressin or pre-treatment with 1 mg dexamethasone improved test specificity, offering promising ways to improve test performance if sensitivity is maintained in CD. CLINICAL TRIAL REGISTRATION NUMBER/BACKGROUND:NCT06635629.

IMPORTANCE/UNASSIGNED:The Centers for Medicare & Medicaid Services requires that health systems offer smoking cessation services to patients undergoing lung cancer screening. However, the most effective methods to achieve smoking cessation among medically underserved patients undergoing lung cancer screening are unknown. OBJECTIVE/UNASSIGNED:To compare the effectiveness of 4 strategies for promoting smoking cessation among medically underserved persons referred for lung cancer screening. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This randomized clinical trial included currently smoking individuals referred for lung cancer screening at 4 US health systems (5 centers) who identified as Black, Hispanic, living in a rural area, or being of low socioeconomic status. The first participant was enrolled on May 17, 2021, and the date of last follow-up was April 29, 2025. INTERVENTION/UNASSIGNED:Patients were randomized to 1 of 4 groups. Participants received either an ask-advise-refer strategy to smoking cessation services (usual care); usual care plus free pharmacotherapy (ie, nicotine replacement and reimbursement for varenicline or bupropion); usual care, free pharmacotherapy, and financial incentives up to $600 contingent on biochemically confirmed smoking cessation; or usual care, free pharmacotherapy, and financial incentives plus a mobile health tool motivating patients to think about their future health. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary end point was biochemically confirmed, sustained tobacco abstinence through 6 months, measured with cotinine, anabasine, or carboxyhemoglobin. RESULTS/UNASSIGNED:Of the 9963 patients assessed for eligibility, 3259 patients were randomized and 3220 were included in the primary analysis. The median (IQR) age was 61.1 (56.6-66.0) years, 1948 (60.3%) were female, 823 (25.5%) were Black, 287 (8.9%) were Hispanic, 1251 (38.8%) lived in rural areas, 1519 (74.9%) had low socioeconomic status, and 1792 (55.5%) reported smoking more than 10 cigarettes per day at enrollment. Sustained tobacco abstinence rates through 6 months were 4.3% with usual care, 5.1% with the addition of pharmacotherapy, 8.8% with the addition of financial incentives, and 7.2% with the addition of mobile health tool. Adding financial incentives increased the adjusted rate of sustained tobacco abstinence compared with usual care (difference, 4.6% [95% CI, 2.1%-7.0%]; P < .001) and usual care plus free pharmacotherapy (difference, 4.1% [95% CI, 1.7%-6.4%]; P < .001). Adding free pharmacotherapy to ask-advise-refer was not superior to ask-advise-refer alone (difference, 0.5% [95% CI, -1.7% to 2.6%]; P = .66). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Among medically underserved adults who currently smoked cigarettes and were referred for lung cancer screening, rates of sustained tobacco abstinence were higher through 6 months with addition of financial incentives compared with ask-advise-refer alone or with addition of free pharmacotherapy. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04798664.

Myocardial strain imaging enables quantification of cardiac deformation. Cardiovascular magnetic resonance imaging (CMR) is well suited for strain assessment due to the ability to image in any given plane with high spatial and contrast resolution. CMR strain measures have incremental diagnostic and prognostic utility over conventional clinical imaging parameters across disease states. Routine integration of CMR strain assessment in clinical practice has been hindered by the lack of agreement on imaging protocols and analysis methods, variability due to noise sensitivity, and a paucity of robust normative age-, sex- and ethnicity-specific reference ranges. In recognition of the expanding applications of strain techniques in clinical and research CMR, this joint SCMR/RSNA/EACVI scientific statement integrates data from original research studies, guidelines, and opinions from experts across the field to guide responsible and evidence-based utilization of CMR strain. © 2026 The Author(s). Published by Elsevier Inc. on behalf of Society for Cardiovascular Magnetic Resonance, by Oxford University Press on behalf of European Society of Cardiology, and by RSNA. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by/4.0/). Supplemental material is available for this article. This paper was jointly developed by Journal of Cardiovascular Magnetic Resonance, European Heart Journal - Cardiovascular Imaging, and Radiology and jointly published by Elsevier Inc, Oxford University Press, and RSNA. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Any citation can be used when citing this article.

Contact dermatitis (CD) is the 5th most common skin disease1 and affects 15-20% of the general population over their lifetimes.2 Currently, the T.R.U.E. TEST® is the only FDA-approved diagnostic product to aid in the diagnosis of Allergic Contact Dermatitis. To address that diagnostic gap, the US Food and Drug Administration held a public workshop in October 2025. These proceedings summarize the workshop presentations and discussions.

Excessive cyclin D1 accumulation is a frequent oncogenic event in head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC). Although classically associated with enhanced proliferation and genomic instability, we revealed that cyclin D1 dysregulation induces metabolic rewiring that leads to unexpected metabolic dependencies. Sustained nuclear retention of cyclin D1 drove metabolic reprogramming through activation of CDK4/6 and downregulation of mitochondrial isocitrate dehydrogenase 3 (IDH3), reducing α-ketoglutarate and NADH production. This metabolic alteration increased glutamine dependence and elevated autophagic flux, and co-targeting autophagy and glutamine metabolism suppressed the growth of squamous cell carcinoma models in vitro and in vivo. Together, these findings highlight a therapeutic strategy for HNSCC and ESCC that leverages metabolic reprogramming induced by dysregulated cyclin D1/CDK4 activity, with potential applicability to patients with tumors refractory to conventional therapies.

Autism affects male individuals four times more often than female individuals, yet the basis of this sex bias remains unclear. One hypothesis is that this sex bias is due to genetic variants in X chromosome genes where haploinsufficiency causes neurodevelopmental disorders (NDDs). In heterozygous XX female probands, a complete loss-of-function variant in one of these genes often causes syndromic NDD, but the same variant is too deleterious for survival in hemizygous XY males. A mild hypomorphic variant, however, may be tolerated in a female carrier but may produce milder neurological phenotypes in a male proband. We tested this by investigating cis-regulatory elements (CREs) of MECP2, a dosage-sensitive gene on the X chromosome where total loss-of-function variants cause Rett syndrome in female children and severe, usually fatal neonatal encephalopathies in male infants. Using a massively parallel reporter assay in human neurons, we mapped transcription factor binding sites within MECP2 CREs and tested autism-associated variants for functional impact. We identified two noncoding variants that change CRE activity and are associated with male-biased autism phenotypes in the proband pedigrees. One of these, a promoter variant, disrupts NFY binding and reduces MECP2 expression by ∼30%, a magnitude that produces social deficits, hyperactivity, and anxiety-like phenotypes in mice. These findings suggest noncoding MECP2 variants can cause idiopathic, male-biased autism and provide a framework for uncovering regulatory variants in other X chromosome neurodevelopmental genes that may contribute to autism's missing heritability.

Myocardial strain imaging enables quantification of cardiac deformation. Cardiovascular magnetic resonance imaging (CMR) is well suited for strain assessment due to the ability to image in any given plane with high spatial and contrast resolution. CMR strain measures have incremental diagnostic and prognostic utility over conventional clinical imaging parameters across disease states. Routine integration of CMR strain assessment in clinical practice has been hindered by the lack of agreement on imaging protocols and analysis methods, variability due to noise sensitivity, and a paucity of robust normative age-, sex- and ethnicity-specific reference ranges. In recognition of the expanding applications of strain techniques in clinical and research CMR, this joint SCMR/RSNA/EACVI scientific statement integrates data from original research studies, guidelines, and opinions from experts across the field to guide responsible and evidence-based utilization of CMR strain.