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An observational study of menstrual function and related hormones before and after treatment of Cushing syndrome

Brown, Brielle M; McGlotten, Raven; Nieman, Lynnette K; Elenius, Henrik
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.
PMCID:13504277
PMID: 42643607
ISSN: 2472-1972
CID: 6074443

Evaluation of desmopressin stimulation test specificity in healthy volunteers

Elenius, Henrik; Brown, Brielle M; McGlotten, Raven; Moore, Casey; Nieman, Lynnette K
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.
PMCID:13482792
PMID: 42535456
ISSN: 2049-3614
CID: 6074442

Aligning treatment to physiology: when to use chronotherapy, block and replace, or titration to treat hypercortisolism

Elenius, Henrik; Findling, James W; Tabarin, Antoine; Nieman, Lynnette K
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.
PMCID:13280641
PMID: 42325498
ISSN: 2472-1972
CID: 6074441

Pancreatic Cancer KRAS Breakthrough: Drug Graveyard No More

Yu, Peter Y; Oberstein, Paul E; Maitra, Anirban; Hidalgo, Manuel
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy and has long been regarded as a therapeutic "drug graveyard", with modest gains from cytotoxic combination chemotherapy and numerous novel agents failing to show benefit in clinical trials. The quest to directly target RAS has moved from concept to reality with the FDA approval of daraxonrasib (Rasonque) for adults with metastatic PDAC who have received at least one prior systemic therapy or are not candidates for multiagent systemic therapy. Here we discuss a wave of clinical trials that are poised to change this narrative and usher in the era of RAS-targeted therapy. Given the flood of compounds and combinations, we focus on therapies that have advanced to phase 3 clinical trials. Collectively, these studies demonstrate how RAS-targeted therapies are poised to transform the PDAC treatment landscape. The current generation of trials will determine whether these emerging strategies can translate into durable survival gains and turn PDAC from a "drug graveyard" into a drug haven for novel therapies.
PMCID:13644853
PMID: 42836735
ISSN: 1557-3265
CID: 6073935

Cardiovascular magnetic resonance derived myocardial strain: applications, acquisition techniques, analysis, and reporting. A Scientific Statement of the Society for Cardiovascular Magnetic Resonance, Radiological Society of North America, and the European Association of Cardiovascular Imaging of the ESC

Gulsin, Gaurav S; Ambale-Venkatesh, Bharath; Axel, Leon; Bluemke, David A; Captur, Gabriella; Cavalcante, João L; Ennis, Daniel B; Epstein, Frederick H; Gerber, Bernhard; Hanneman, Kate; Kawel-Boehm, Nadine; Kelle, Sebastian; Kramer, Christopher M; Lima, Joao A C; Lamb, Hildo J; Lu, Minjie; Marwick, Thomas H; Romano, Simone; Young, Alistair A; McCann, Gerry P
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.
PMID: 42855356
ISSN: 1532-429x
CID: 6074074

Cardiovascular Magnetic Resonance derived Myocardial Strain: Applications, Acquisition Techniques, Analysis, and Reporting. A Scientific Statement of the Society for Cardiovascular Magnetic Resonance, Radiological Society of North America, and European Association of Cardiovascular Imaging of the ESC

Gulsin, Gaurav S; Ambale-Venkatesh, Bharath; Axel, Leon; Bluemke, David A; Captur, Gabriella; Cavalcante, João L; Ennis, Daniel B; Epstein, Frederick H; Gerber, Bernhard; Hanneman, Kate; Kawel-Boehm, Nadine; Kelle, Sebastian; Kramer, Christopher M; Lima, João A C; Lamb, Hildo J; Lu, Minjie; Marwick, Thomas H; Romano, Simone; Young, Alistair A; McCann, Gerry P
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.
PMID: 42852923
ISSN: 1527-1315
CID: 6074048

Public Awareness and Perceptions of Stem Cell Therapy for Stroke: A Cross-Sectional Survey Study

Kumar, Shreya P; Kumar, Prasanna V
Background Stroke remains a leading cause of death and long-term disability. Although stem cell-based approaches are being investigated as possible regenerative strategies for stroke, public perceptions of their potential benefits, risks, mechanisms, and clinical use are not well-characterized. This exploratory survey described responses to an investigator-developed questionnaire about stem cell therapy for stroke. Methods A 10-item cross-sectional questionnaire was distributed electronically through Google Forms (Google, Inc., Mountain View, CA) to 36 individuals in a convenience sample; 26 completed questionnaires were received (response rate: 72.2%). The questionnaire was investigator-developed and was not validated as a measure of factual knowledge, clinical efficacy, or safety. Responses were categorized as "yes," "no," or "maybe"; one item used time-based response categories. Counts and percentages were calculated using the total number of completed questionnaires as the denominator. The survey was independently conducted as a student-led summer academic project and did not undergo review by an institutional review board, school ethics committee, or independent ethics authority. Results Twenty-six responses were analyzed. For the item asking whether embryonic stem cells are effective in stroke treatment, eight respondents (30.77%) selected "yes," 16 (61.54%) selected "maybe," and two (7.69%) selected "no." For the item asking whether stem cell treatment has advantages for stroke, 21 respondents (80.77%) selected "yes," four (15.38%) selected "maybe," and one (3.85%) selected "no." "Maybe" was the majority or joint-most-frequent response for six of 10 items, including items about animal testing, adverse effects, alternative regenerative treatments, and use during pregnancy. Conclusions In this small convenience sample, responses to an investigator-developed questionnaire suggested favorable perceptions of possible benefits of stem cell therapy for stroke, alongside frequent uncertainty about safety, mechanisms, the timing of improvement, and use in special populations. Because the questionnaire was not validated as a factual-knowledge instrument, findings should be interpreted strictly as descriptive perceptions rather than as evidence of respondents' medical knowledge, treatment confidence, or the clinical efficacy or safety of stem cell therapy. Larger studies using validated instruments and representative sampling are needed.
PMCID:13634582
PMID: 42831189
ISSN: 2168-8184
CID: 6073881

Smoking Cessation Among Underserved Patients Referred for Lung Cancer Screening: A Randomized Clinical Trial

Hart, Joanna L; Vachani, Anil; Neslund-Dudas, Christine M; Gould, Michael K; Facktor, Matthew A; Blady, Shira; Bayes, Brian A; Sheu, Dorothy; Madden, Vanessa L; Ferrante, Emma Britez; Patel, Nirali; Tian, Jenny; Whitman, Casey; Creekmur, Beth; Kohn, Rachel; Simoff, Michael J; Volpp, Kevin G; Small, Dylan; Scott, Michael E; Holm, Amanda L; Stephens Shields, Alisa J; Halpern, Scott D
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.
PMID: 42832220
ISSN: 1538-3598
CID: 6073891

Medicare and Bureau of Health Workforce and Funded Primary Care Residency Positions

Hayes, Rachael W; Dapkins, Isaac P
PMID: 42832212
ISSN: 1538-3598
CID: 6073890

Cardiovascular magnetic resonance derived myocardial strain: applications, acquisition techniques, analysis, and reporting

Gulsin, Gaurav S; Ambale-Venkatesh, Bharath; Axel, Leon; Bluemke, David A; Captur, Gabriella; Cavalcante, João L; Ennis, Daniel B; Epstein, Frederick H; Gerber, Bernhard; Hanneman, Kate; Kawel-Boehm, Nadine; Kelle, Sebastian; Kramer, Christopher M; Lima, Joao A C; Lamb, Hildo J; Lu, Minjie; Marwick, Thomas H; Romano, Simone; Young, Alistair A; McCann, Gerry P
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.
PMID: 42851042
ISSN: 2047-2412
CID: 6074040