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Department/Unit:Medicine
Coccidioidomycosis Masquerading as Malignancy: A Case of Mediastinal Mass and Pericardial Effusion in an Immunocompetent Jamaican Male
Governor, Samuel B; Zaidi, Maira; Nepali, Prakash; Grigorova, Yulia; Baissari, Amali; Toussaint, Richard; Dabaghyan, Mariam; Melendez-Garcia, Alberto; Jammal, Rita
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.
PMCID:12910321
PMID: 41710067
ISSN: 2090-6625
CID: 6074469
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
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
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
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
Outpatient step-up dosing of teclistamab and talquetamab in relapsed or refractory
Shah, Kunal; Forrest, Paul; Garg, Ananya; Kolluru, Pranav; Kaminetzky, David; Morgan, Gareth J; Braunstein, Marc; Lahoud, Oscar; Davies, Faith E
BACKGROUND:Bispecific T-cell-engaging antibodies against BCMA and GPRC5D demonstrate high efficacy in relapsed/refractory multiple myeloma (RRMM) but are associated with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), traditionally prompting inpatient monitoring when commencing therapy. Contemporary step-up dosing and prophylactic strategies may enable safe outpatient administration. PATIENTS AND METHODS/METHODS:We conducted a single-center retrospective study evaluating outpatient step-up dosing (SUD) of teclistamab or talquetamab in adults with RRMM. Patients met institutional outpatient eligibility criteria and received standard pre-medications; prophylactic tocilizumab was administered at physician discretion. The primary endpoint was incidence and severity of CRS/ICANS. Secondary endpoints included SUD completion, healthcare utilization, and need for hospitalization. RESULTS:Thirty-eight patients underwent 43 outpatient SUD initiations (teclistamab n = 30; talquetamab n = 13). Median age was 72 years, and disease burden was high. SUD completion occurred in 93%. CRS occurred in 26% of initiations and was exclusively grade 1-2; no grade ≥ 3 CRS occurred. One possible grade III ICANS event (2%) occurred after completion of SUD. CRS incidence was similar with and without prophylactic tocilizumab (29% vs 32%). Most events occurred during the first two step-up doses. Hospitalization occurred in 5 (12%) SUD initiations for CRS/ICANS events and overall healthcare utilization was modest. CONCLUSION/CONCLUSIONS:Outpatient administration of teclistamab and talquetamab SUD in RRMM is feasible and safe with low rates of low-grade CRS. Toxicities occur early and are manageable with structured monitoring, supporting outpatient delivery in appropriately selected patients.
PMID: 42837800
ISSN: 1873-5835
CID: 6073941
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
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
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