Citations

Abstract Context Crinecerfont, a first-in-class corticotropin-releasing factor type 1 receptor antagonist, is FDA-approved as an adjunct to the physiologic glucocorticoid (GC) required to treat the underlying adrenal insufficiency in patients (≥4 years old) with classic congenital adrenal hyperplasia (CAH). By reducing elevated adrenocorticotropic hormone, crinecerfont controls excess adrenal androgens, thereby enabling lower GC doses. However, there are no published recommendations for how to reduce supraphysiologic GC doses after initiating crinecerfont. This manuscript aims to provide a framework developed by experienced endocrinologists for reducing supraphysiologic GC doses in patients taking crinecerfont. Evidence Acquisition An experienced panel of 11 endocrinologists discussed strategies and considerations when reducing GC doses and developed an algorithm to guide GC dose reductions after introducing crinecerfont in adults with CAH. Evidence Synthesis Approaches to GC reduction should be individualized based on the patient's therapeutic goals, cortisol needs, lifestyle preferences, and the clinician's experience to set appropriate targets for clinical parameters, androgens, and GC dose regimen. In general, GC doses should be reduced gradually to minimize the risks of developing symptoms of GC withdrawal or adrenal insufficiency. GC doses should be adjusted to the lowest level needed to maintain androgens at goal, without reducing below what is needed for cortisol replacement. Practical considerations during GC dose reduction include switching from longer- to shorter-acting GCs (eg, from dexamethasone to hydrocortisone), optimizing dose distribution to mimic normal circadian cortisol exposure, and consolidating or eliminating doses to improve adherence. Conclusion This framework for reducing supraphysiologic GC doses in adult patients taking crinecerfont may become increasingly relevant as treatment of CAH shifts toward physiologic GC replacement with adjunctive control of adrenal androgens.

Normothermic regional perfusion (NRP) adoption for donation after circulatory death (DCD) liver transplantation in the United States has been growing, but there remains a higher rate of non-utilization of NRP DCD liver grafts as compared with donation after brain death liver grafts. Six transplant centers and 1 organ procurement organization (OPO) with substantial NRP liver procurement experience performed retrospective reviews of all NRP procurement attempts from September 1, 2021, until March 1, 2024, identifying opportunities for utilization. Five of the 6 transplant centers had prospectively collected data on all accepted livers with NRP intent. The transplant center's intention to utilize DCD donors included 329 livers accepted for transplantation before withdrawal, 252 (76.6%) potential donors expired within the hospital timeframe for donation, and 168 (66.7%) livers were transplanted. Fifty-seven opportunities for utilization were identified by transplant centers, plus 11 from the OPO: most were due to exceeding a functional warm ischemic time limit (n=26), other reasons (n=17), and functional assessment (n=16). The lessons learned by centers in this study provide guidance for newer NRP centers and for OPOs in identifying opportunities for utilization of NRP DCD grafts that have historically been declined.

Hypertension is the main risk factor for cardiovascular disease (CVD), affecting 20–40% of Latin American (LATAM) adults, and responsible for more than two million deaths annually due to CVD. The different ethnic, economic, geographic, and cultural characteristics of the LATAM population influence the high prevalence of all cardiovascular risk factors (CVRF), particularly metabolic disturbances such as type 2 diabetes (DM2), obesity and the metabolic syndrome. Their main determinants in LATAM includes environment, food quality, social inequity, low education, political aspects, contextual behaviour, and genetics. The prevalence of overweight and obesity in LATAM increased during the last four decades reaching figures of 10–20% in childhood, 30–40% in adolescence, and 60–70% in adults. Many studies in the region have reported the extremely low rates of awareness, treatment, and control of CVRF in the general population of LATAM, particularly in patients with metabolic disorders, and the consequent high cardiovascular morbidity and mortality. This 2026 LATAM consensus is developed by a large group of experts from different LATAM countries, the USA and Europe, representing areas of internal medicine, cardiology, nephrology, endocrinology, geriatrics, paediatrics, pharmacology, and epidemiology. A careful search for novel studies in LATAM, together with new evidence that has emerged since the 2019 LATAM consensus, support the statements and recommendations in the current report. This update aims to provide clear and useful recommendations for health professionals to improve awareness, treatment, and control of hypertension and associated CVRF in the region.

Abstract Background IDH-mutant astrocytomas are classified as WHO grade 4 in the presence of conventional high-grade histologic features and/or homozygous CDKN2A/B deletion in the 5th edition of the WHO Classification of Central Nervous System Tumour guidelines. However, work over the past decade has indicated a number of other molecular alterations that warrant consideration as potential prognostic markers. Methods We used univariate Kaplan-Meier and multivariate Cox proportional hazards regression analysis to evaluate the prognostic effects of homozygous CDKN2A/B deletion, CDK4 amplification, CCND2 amplification, PDGFRA amplification/mutation, PIK3R1 mutation, PIK3CA mutation, MYCN amplification, EGFR amplification/mutation, TERT promoter mutation, and grade 4 histologic features in two independent cohorts of WHO grade 2-4 IDH-mutant astrocytoma (n = 840 and n = 367). Results The presence of CDK4 amplification, CCND2 amplification, PDGFRA alteration, PIK3R1 mutation, MYCN amplification, and EGFR alteration were each associated with reduced overall survival compared to WHO grade 2/3 astrocytomas without these molecular features. 17.7% (148/837) of otherwise grade 2/3 astrocytomas had one or more of these molecular criteria, with resulting intermediate clinical outcome in terms of overall survival (median survival of 67.3-82.0 months) compared to grade 2/3 astrocytomas without these molecular features (median survival of 135.0-140.7 months) and grade 4 astrocytomas (median survival of 35.3-45.0 months). Conclusions The presence of CDK4, CCND2, PDGFRA, PIK3R1, MYCN, and EGFR alterations result in an intermediate patient survival in IDH-mutant astrocytoma. Adding these molecular alterations should be considered in future diagnostic classification systems to improve stratification of high-risk patients.

Abstract Endogenous Cushing syndrome (CS) is a rare disorder resulting from chronic exposure to excessive concentrations of cortisol. It is likely underdiagnosed because many clinical signs and symptoms are non-specific and overlap with those of common conditions. Furthermore, biochemical testing to diagnose CS can be complex and challenging, especially in milder cases. CS is characterized by excessive daily cortisol production, but it is also associated with a disrupted circadian rhythm of cortisol secretion. Traditional cortisol monitoring techniques rely on single-time-point measurements or a cumulation of measurements, which are unable to capture the complete daily rhythm of cortisol fluctuations. Currently, the utility of assessing individual patients’ cortisol circadian rhythm during diagnosis and treatment of CS is not well characterized. In this review, we will discuss how cortisol is measured in clinical practice and the potential benefit of measurement and normalization of the cortisol circadian rhythm.

Abstract Background Head and neck cancer represents the seventh most common cancer diagnosis globally. Maintaining sufficient nutrition is important for preventing malnutrition (undernutrition) and muscle wasting, which contribute to worse outcomes, although many patients are unable to maintain adequate oral intake throughout treatment. This guideline provides practice guidance on nutrition care for patients with head and neck cancer. Methods An interdisciplinary team developed key questions and scanned results from a systematic search of the PubMed, EMBASE, CINAHL, and Cochrane Central databases back to 2001. Recommendations were created for key questions concerning timing and duration of nutrition support (early vs delayed enteral nutrition [EN], postoperative feeding, and perioperative dietitian intervention), frequency of dietitian and speech pathology consultations, nutrition screening and assessment, macronutrient requirements, enteral access devices, adjunctive strategies (appetite stimulants and continuation of oral intake alongside EN), specialized nutrients (arginine, glutamine, ω‐3, and immunonutrition), and interdisciplinary care. Results Ninety‐two studies were included. Recommendations were made supporting early initiation of EN when oral intake is inadequate, nutrition within 24 h after surgery, weekly consultation with a dietitian during radiotherapy, malnutrition screening and assessment with validated tools, interdisciplinary models of care, dietitian involvement before and after surgery, and when to consider use of specialized nutrients. Recommendations are also provided for protein intake (1.2–1.5 g/kg/day) and energy intake (≥30 kcal/kg/day). Conclusion This guideline provides guidance for the nutrition care of patients with head and neck cancer, identifies research gaps, and calls for standardized outcome reporting to further the state of the evidence. This paper was approved by the ASPEN Board of Directors.

Abstract Background Cardiomegaly is a clinically significant incidental finding on chest computed tomography (CT) associated with heart failure, arrhythmias, and sudden cardiac death. Qualitative radiologist assessment is variable, and automated AI tools may enable objective opportunistic cardiac volumetry. Purpose To evaluate whether AI-enabled total cardiac volume (TCVAI) derived from non-ECG-gated, non-contrast chest CT can identify cardiomegaly as defined by echocardiography. Materials and Methods This retrospective study included 307 consecutive patients (median age, 67 years; 56% male) who underwent non-contrast chest CT at a single center on 7 scanner types (4 vendors) and clinically indicated echocardiography within 31 days. A commercially available AI tool (AI-Rad Companion, Siemens Healthineers) automatically quantified TCVAI, indexed to body surface area (TCVAI/BSA). Echocardiography reports were reviewed for chamber dilation and left ventricular hypertrophy (LVH), collectively defined as cardiomegaly. Associations between TCVAI/BSA and echocardiographic findings were assessed using correlation, ordinal regression, and receiver operating characteristic (ROC). Interscan repeatability was evaluated in 248 patients with 544 repeat CT examinations. Prespecified sex-specific thresholds were tested in a temporally independent validation cohort of 50 patients. Results Median TCVAI was higher in patients with cardiomegaly than those without (1061.9 vs 798.4 mL; P < .001). TCVAI/BSA was associated with chamber dilation and LVH severity on univariate analysis and remained associated in multivariable ordinal models, except for right ventricular dilation. Discriminatory performance was fair to good, with area under the curve (AUC) 0.81 (95% CI, 0.75-0.87) in men and 0.77 (95% CI, 0.69-0.85) in women. Interscan repeatability was excellent (intraclass correlation coefficient [ICC]: 0.93). In independent validation, performance ranged from sensitivity 89.3%/specificity 27.3% at a high-sensitivity threshold to sensitivity 28.6%/specificity 100% at a high-specificity threshold. Conclusion AI-derived cardiac volume from routine chest CT shows fair to good performance for identifying echocardiography-defined cardiomegaly with high measurement repeatability, supporting a potential role for automated cardiac volumetry as an objective, opportunistic biomarker.