BACKGROUND:Hyperuricemia has traditionally been viewed primarily as a cause of gout; however, accumulating evidence indicates that elevated serum uric acid (sUA) is also associated with increased cardiovascular and renal risk. Recent epidemiological studies suggest that adverse outcomes may occur at sUA levels well below the classic crystal-based thresholds, particularly in patients with high cardiovascular risk. METHODS:This expert consensus document was developed by a multidisciplinary European panel of cardiology, internal medicine, nephrology, and hypertension specialists. The recommendations are based on a critical narrative review of the literature published, including large cohort studies, meta-analyses, randomized controlled trials, and contemporary European guidelines (ESC, ESH, KDIGO, EULAR). Particular emphasis was placed on outcome-driven serum urate thresholds and clinically applicable risk stratification. RESULTS:Hyperuricemia is common and increasingly prevalent, especially among individuals with hypertension, chronic kidney disease, obesity, diabetes, and established cardiovascular disease. Elevated sUA is independently associated with cardiovascular mortality, heart failure, stroke, and faster progression of chronic kidney disease. However, randomized trials have not shown clear cardiovascular or renal benefit from routine urate-lowering therapy in patients with asymptomatic hyperuricemia. Based on current evidence, this consensus proposes a risk-based, individualized approach to hyperuricemia management and presents a pragmatic six-rung therapeutic ladder integrating lifestyle measures, optimization of comorbidities, and pharmacological urate-lowering therapy when clinically indicated. CONCLUSIONS:Hyperuricemia should be recognized as a relevant cardiovascular and renal risk factor rather than a benign biochemical finding. Serum urate measurement can improve risk stratification in selected high-risk populations. While routine treatment of asymptomatic hyperuricemia cannot be universally recommended, targeted urate-lowering strategies may be appropriate in patients with high cardiovascular risk, symptomatic disease, or very high sUA levels. Future randomized trials are needed to define whether urate-lowering therapy can improve hard cardiovascular and renal outcomes in these populations.
Ultrasound has become indispensable in the management of patients supported with extracorporeal membrane oxygenation (ECMO), enabling rapid diagnosis, procedural guidance, physiologic monitoring, and informed decision-making across the entire ECMO continuum. This review, conducted under the auspices of the Extracorporeal Life Support Organization (ELSO), provides evidence-based recommendations for the use of ultrasound in adult, pediatric, and neonatal ECMO patients. An international, multidisciplinary panel of experts with dual expertise in ECMO and ultrasound, representing all ELSO chapters, convened to define the scope and structure of the review. A comprehensive literature review identified 133 relevant publications informing recommendations. The review addresses training and competency requirements, choice of ultrasound modalities, and the role of ultrasound before ECMO initiation, during cannulation, throughout ECMO support, for troubleshooting complications, and during ECMO weaning and post-decannulation care. Pre-ECMO ultrasound is emphasized for assessment of cardiopulmonary function, vascular anatomy, and identification of contraindications or reversible conditions. Real-time ultrasound guidance is recommended for cannulation to reduce complications and confirm optimal cannula positioning. During ECMO, echocardiography and extracardiac ultrasound are central to monitoring cardiac function, cannula position, ventricular loading conditions, pulmonary pathology, neurological complications, and vascular integrity. Ultrasound-based strategies for diagnosing hypoxemia, recirculation, tamponade, ventricular distension, and limb ischemia are detailed. Finally, ultrasound plays a critical role in assessing readiness for ECMO liberation and identifying post-ECMO complications. This review highlights the pervasive role of ultrasound as a core competency in ECMO care and provides a practical framework to support safe, effective, and standardized ultrasound use across diverse ECMO programs worldwide.
BACKGROUND:Intramedullary melanocytoma of the spinal cord is an extremely rare primary melanocytic tumor, with less than 30 cases reported worldwide. Although histologically benign, these lesions may show locally aggressive behavior and a tendency for recurrence. We report an unprecedented case of multifocal intradural extramedullary recurrence following resection of an intramedullary melanocytoma, an occurrence not previously described in the English-language literature. CASE PRESENTATION:A 70-year-old woman presented with rapidly progressive weakness and sensory loss in both lower limbs. Four years earlier, she had undergone total resection of a histologically confirmed intramedullary melanocytoma of the conus medullaris. Current MRI revealed multiple intradural extramedullary lesions extending from the midthoracic to sacral levels, the largest at T5 and T11-T12, causing severe spinal cord compression. The lesions were hyperintense on T1-weighted, hypointense on T2-weighted and markedly hyperintense on T1 SPIR images, consistent with leptomeningeal dissemination of a melanocytic tumor. No intracranial lesions were detected. Given the extensive spinal involvement, further invasive diagnostics or radiotherapy were not indicated, and palliative management with corticosteroids and rehabilitation was initiated. The patient experienced gradual neurological deterioration with early spasticity and minimal partial recovery. CONCLUSIONS:This case demonstrates that even histologically benign spinal melanocytomas can behave destructively and disseminate along the leptomeninges. Awareness of this potential, combined with long-term whole-neuraxis MRI surveillance, is crucial for early detection and timely management. The report highlights the unpredictable clinical course of these rare tumors and the need for individualized multidisciplinary care.
Diagnosing ovarian sex cord-stromal tumors can be difficult in some cases due to the overlapping morphologic and immunohistochemical (IHC) features, especially for adult granulosa cell tumors (AGCTs), juvenile granulosa cell tumors (JGCTs), Sertoli-Leydig cell tumors (SLCTs), and thecomas. In such situations, molecular testing can be helpful, as these tumors are often associated with specific genetic alterations. SLCTs, for instance, are known to be associated with DICER1 mutations. However, expression of DICER1 has not yet been systematically investigated in sex cord-stromal tumors. We evaluated the potential use of DICER1 IHC for detecting DICER1 mutations in ovarian sex cord-stromal tumors, including 267 AGCTs, 38 SLCTs, 5 JGCTs, and 21 Leydig cell tumors/steroid cell tumors (SCTs). Specifically, DICER1 positivity was found in 21 of 38 (55.3%) of SLCTs and 16 of 21 (76.2%) of SCTs. All DICER1-positive moderately differentiated SLCTs harbored a DICER1 mutation. One DICER1-negative moderately differentiated SLCT carried 2 DICER1 mutations. Additionally, 3 of 10 well-differentiated SLCTs showed IHC positivity. No SCT harbored a DICER1 mutation. Among AGCTs, 4 of 267 (1.5%) were DICER1 positive, and 1 of these cases harbored 2 DICER1 mutations. No JGCT demonstrated a DICER1 mutation or expression. In cases with both analyses available, DICER1 expression was found in 39 of 273 (14.3%), whereas 21 of 273 (7.7%) harbored a DICER1 mutation. Using an optimal cutoff of ≥10% positive tumor cells, IHC closely matched mutational status (sensitivity of 90.5%, specificity of 92.1%). Our study found substantial concordance between DICER1 IHC and mutation status in a subset of sex cord-stromal tumors, suggesting that IHC detection of DICER1 protein may serve as a useful surrogate marker for DICER1 mutation, especially in SLCTs and AGCTs. This could be particularly valuable in settings where molecular testing is limited by cost and/or availability. However, in SCTs, the DICER1 expression is common but unrelated to DICER1 mutation. This suggests that alternative mechanisms, potentially involving androgen-related pathways, may contribute to DICER1 expression in these tumors.
Low-grade endometrial stromal sarcomas (LGESS) and endometrial stromal nodules represent a distinct entity with characteristic morphology, immunohistochemical profile, and molecular features. It has been suggested that the activation of the Wnt signaling pathway is a potential driver in some of these tumors. Approximately 70-75% of LGESS are characterized by non-random recurrent fusions mostly involving JAZF1 and PHF1 genes. Although the exact mechanism remains unclear, activation of the Wnt signaling pathway appears to be related to the functional deregulation of chromatin remodeling complexes caused by these fusion proteins. However, knowledge about other possible mechanisms and recurrent molecular alterations occurring at the DNA level in LGESS remains limited. We report three cases of LGESS in patients aged 39, 49, and 50, lacking recurrent fusions but harboring CTNNB1 mutations in exon 3 as the sole detectable molecular alteration. One case had morphological features of typical LGESS (in some areas with perivascular whorling, which was not a dominant feature), the second case showed features of the fibroblastic variant of LGESS, and the third case comprised a LGESS with a peculiar morphology with diffuse whorling morphologically identical to the recently described entity endometrial stromal tumor with GREB1::CTNNB1 fusion. RNA-Seq-based clustering analysis of the three cases and a set of 193 uterine tumors showed that the CTNNB1-mutated cases clustered near LGESS cases. This study adds to the growing body of evidence that CTNNB1 mutations represent a driver molecular event in a small subset of endometrial stromal tumors. Moreover, the results of our study suggest that tumors with CTNNB1 mutation and GREB1::CTNNB1 fusion may exhibit identical morphology and potentially represent the same category of tumor. Characterization and reporting of additional cases are needed to determine whether these are part of the spectrum of low-grade endometrial stromal tumors (either endometrial stromal nodule or LGESS) or represent a separate category of tumors characterized by CTNNB1 alteration as a driver event.
