Fundación Santa Fe de Bogotá

ABSTRACT Maintaining electrical signaling homeostasis in the human neocortex relies on cell-type specific gene expression programs. However, when these programs are disrupted, the resulting imbalances can contribute to the pathogenesis of neurological disorders like epilepsy. Genetic factors are particularly implicated in a specific subtype of epilepsy known as refractory epilepsy or drug-resistant epilepsy (RE/DRE). This study shows the main results of the analysis of single cell transcriptomics for five pediatric RE patients in Colombia. A total of six samples obtained through surgical resection were analyzed by single-nuclei RNA sequencing (snRNA-seq). The genome of one patient was sequenced using high fidelity long-read sequencing. Functional enrichment of differentially expressed genes (DEGs) revealed glia-driven dysregulation of synaptic signaling, impaired glial–neuronal communication, and altered expression of genes related to neurotransmitter transport and calcium signaling. Activation of taste receptors in neurons was associated with neuroinflammatory processes. Structural variants were detected in genes associated with alterations of expression in specific cell types. This new data resource increases the diversity of information needed to develop new strategies for diagnosis of refractory epilepsy.

<h2>ABSTRACT</h2><h3>Objectives</h3> Global rheumatology training faces immense challenges, with over 1.7 billion people affected by musculoskeletal diseases and pronounced regional disparities in specialist access. Diverse curricula, resource limitations, and variable career pathways underscore the urgency for targeted harmonisation efforts. This study aims to present a vision for harmonising rheumatology training worldwide, highlighting the contributions of continental societies and innovative young networks, based on insights from the EMerging European Alliance of Associations for Rheumatology (EULAR) NETwork (EMEUNET) Presents session at EULAR Congress 2025 ‘Rheumatology Training Around the Globe'. <h3>Methods</h3> A narrative review of current training models across Africa, Asia-Pacific, Pan-America, and Europe using data from EULAR 2025 Congress supplemented with session slides and speaker insights. <h3>Results</h3> Programmes in Africa remain limited and fragmented, with severe workforce shortages and few structured training opportunities; regional responses include Young African Rheumatologists Network and select international partnerships. Asia-Pacific features multicountry, exam-based curricula governed centrally, but faces shortfalls in infrastructure and fellowship access, addressed in part by Asia Pacific League of Associations for Rheumatology-Young Rheumatology's educational initiatives. Pan-America is marked by significant programme heterogeneity and access barriers, with the United States standing out for its highly structured American College of Rheumatology-accredited programmes, robust educational events, and comprehensive resources. Pan-American League of Associations for Rheumatology Joven and digital education initiatives are reducing training gaps and advancing collaboration. Europe combines robust, competency-focused national programmes, with EULAR and European Union of Medical Specialties actively supporting harmonisation despite persistent local variation, and EMEUNET enhancing mentorship and career support. <h3>Conclusions</h3> Future harmonisation in rheumatology training requires flexible, competency-driven frameworks, expanded digital platforms, multilevel mentorship, and sustainable investment, integrating national programmes into global networks.

ABSTRACT.Dengue is a viral disease with a broad spectrum of clinical manifestations. Its severity is associated with risk factors such as periods of endemicity, although the extent of this contribution is unclear. In the present study, the characteristics of the clinical course and differences in the occurrence of severe and lethal outcomes were assessed by the degree of endemicity in patients with dengue treated in health institutions in Cali, Colombia, between 2019 and 2022. A longitudinal, observational-historical, single-cohort study was conducted. Analysis involved evaluating clinical complications during epidemic and endemic periods. Mortality, cumulative incidence of hospital or intensive care unit (ICU) admission, and survival time were estimated using the competing risks method. A total of 1,038 dengue cases were included. Patients with severe dengue and those with warning signs (WS) were consulted up to 6 or 5 days after symptom onset, respectively. A hospital stay of 2.0 days (Quartile [Q]1–Q3: 2–4 days) and an ICU stay of 4.5 days (SD ± 3.9 days) were estimated. A mortality rate of 5.5% was obtained for severe dengue, and a mortality rate of 0.4% was identified for patients with WS. In 2020 and 2021, the probability of hospitalization was 20% from initial contact. The likelihood of dying within 10 days after initial contact was 0% in 2019 and 11.2% (95% CI: 4.0–22.5%) in 2020. The incidence of hospitalization, number of hospital days, and ICU stays due to dengue varied by epidemiological year in a high-endemicity area. The probability of severe and lethal clinical outcomes was higher during 2020 and 2021.

The colonization of the infant gut microbiome during the critical window of 0-3 years is influenced by a multitude of prenatal, environmental and host factors, and may be crucial for life-long health. The infant gut microbiome is highly dynamic, with bifidobacteria-dominance generally established during birth and lactation, followed by transition to a more stable and adult-like composition reached around 3 years of age. Bifidobacteria-dominance in infancy is considered protective as they not only display both anti-inflammatory and immunomodulatory effects but also foster the establishment of other beneficial species via cross-feeding interactions. As predominance of bifidobacteria is considered the marker of a healthy breastfed infant, the use of bifidobacteria-based probiotics for the prevention of gut dysbiosis and related conditions has been investigated. This clinically oriented summary highlights the unmet research needs of Bifidobacterium animalis subsp. lactis, BB-12® (BB-12), a well-studied probiotic added to baby formulas, dietary supplements, and fermented milk products; several potentially beneficial attributes, including acid and bile tolerance, strong adherence properties, pathogen inhibition, and immune modulation are considered. Clinical studies have demonstrated the safety and beneficial effects of BB-12 in infants and children across multiple disorders and highlight the need for improved clinical and regulatory guidelines.

Exosomes are nanoscale extracellular vesicles that transfer proteins, nucleic acids, and lipids, reflecting the state of their parent cells. A persistent scientific challenge is that tumor-derived exosomes (TDEs) facilitate immune evasion, remodel the tumor microenvironment, and create premetastatic niches, intensifying tumor aggressiveness and undermining therapeutic efficacy, ultimately narrowing treatment options to palliative strategies in advanced settings. Yet their dual roles as suppressive agents and potential therapeutic tools remain poorly integrated within current cancer immunotherapy frameworks. This review examines the molecular mechanisms underlying TDE-mediated immune suppression and therapeutic resistance, while also highlighting engineering strategies to exploit or counteract exosome biology. Exosomes derived from chimeric antigen receptor (CAR) T cells preserve antigen specificity and cytotoxic components without the risks of uncontrolled proliferation or cytokine release, offering a safer class of cell free immunotherapies. Advances in genetic engineering, hybrid vesicle design, and nanotechnology have extended exosome applications to the delivery of CRISPR/Cas systems, chemotherapeutic agents, immunoregulatory RNAs, and vaccines, with liposome or nanoparticle integration enhancing targeting and efficacy. Remaining obstacles include the lack of standardized protocols, scalability issues in production, and unresolved regulatory frameworks. Drawing on The Art of War, exosomes can be envisioned as avatars of strategy, discreet messengers capable of undermining host defenses while simultaneously carrying the potential to redirect immunity against the tumor. By embodying both deception and counterattack, they illustrate the capacity to penetrate hidden barriers and redefine the therapeutic battlefield, opening new horizons for precision cancer immunotherapy.Graphical abstract

Primary cardiac tumors are rare, with an incidence of less than 0.33%, and the majority are benign. Sarcomas account for approximately 75% of malignant cardiac tumors, while myxofibrosarcomas represent less than 5% of these cases, making them extremely uncommon. This case report was prepared following the CARE guidelines to ensure comprehensive and transparent reporting and aims to describe the diagnostic and therapeutic challenges of cardiac myxofibrosarcoma. A 60-year-old woman with no relevant medical history complained of epigastric pain, dyspnea, and diaphoresis, leading to a diagnosis of non-ST-elevation myocardial infarction. Transthoracic echocardiography revealed a heterogeneous 3.2 × 3.0 cm mass attached to the atrial side of the anterior mitral valve leaflet, which was subsequently surgically removed. Histological examination of the resected mass identified abundant fibrin, vascular proliferation, and sparse cellularity without definitive evidence of malignancy, suggesting an organized intracardiac thrombus as a differential diagnosis. Four months later, the patient developed progressive dyspnea, orthopnea, and fatigue. Further evaluation with cardiac magnetic resonance imaging revealed a recurrent 4.4 × 4.0 cm mass in the left atrium, obstructing mitral inflow. A second surgical resection and valve replacement were performed. The histopathological analysis identified polygonal and spindle-shaped myofibroblasts embedded in a myxoid stroma with scattered lymphocytes, plasma cells, and focal necrosis. Immunohistochemical staining showed focal positivity for Smooth Muscle Actin, CD34, and p53, with negative staining for h-caldesmon, myogenin, CKAE1/3, CD117, S100, calretinin, MDM2, calponin, D2-40, MyoD1, and CD31confirming the diagnosis of myxofibrosarcoma. Cardiac myxofibrosarcomas are rare but aggressive tumors with a potential for recurrence. This case highlights the diagnostic challenges posed by their atypical presentation and the risk of initial misdiagnosis. Regular follow-up using multimodal imaging, particularly cardiac magnetic resonance, is crucial for early detection and timely intervention of recurrence. A multidisciplinary approach involving cardiologists, radiologists, pathologists, and cardiac surgeons is essential to optimize diagnosis, treatment, and long-term outcomes.

Abstract Background Recurrent acute myocarditis is an uncommon clinical scenario that may suggest the presence of an underlying genetic cardiomyopathy. Case summary A 30-year-old woman presented to the emergency department with recurrent acute myocarditis in 2020 and 2022 and presented to the consult with chest pain in 2023. A syndromic diagnostic workup ruled out infectious, autoimmune, and toxic etiologies. Cardiac magnetic resonance imaging revealed subepicardial and mid-myocardial edema and fibrosis, predominantly affecting the left ventricle, which was subsequently confirmed by an endomyocardial biopsy showing chronic inflammation and interstitial fibrosis. Genetic testing ultimately identified a pathogenic partial deletion in the desmoplakin cardiomyopathy DSP gene, establishing the underlying cause. Management included antiarrhythmic therapy, genetic counseling, lifestyle modifications, and the implantation of a cardioverter-defibrillator Discussion Desmoplakin cardiomyopathy is a genetic disorder that can mimic recurrent myocarditis through inflammatory “hot phases.” Recognition of this phenotype is essential in patients with recurrent myocarditis, especially when imaging findings show left-dominant fibrosis and arrhythmic features. Early diagnosis has important implications for treatment, prognosis, and prevention of sudden cardiac death.