Generative artificial intelligence (GenAI) enables the production of coherent and contextually relevant text by processing large-scale linguistic datasets. Tools such as ChatGPT, Gemini, Claude, and LLaMA are increasingly integrated into medical education, assisting students with a range of tasks, including clinical reasoning, literature review, scientific writing, and formative assessment. Although these tools offer significant advantages in terms of productivity, personalization, and cognitive support, their impact on critical thinking—a cornerstone of medical education—remains uncertain. The aim of this viewpoint paper is to critically assess the influence of GenAI on critical thinking within medical training, examining both its potential to enhance cognitive skills and the risks it poses to cognitive autonomy. Users have reported increased efficiency and improved linguistic output; however, concerns have also been raised regarding the risk of cognitive overreliance. Current evidence presents a mixed picture, indicating both improvements in learner engagement and potential drawbacks such as passivity or susceptibility to misinformation. Without curricular integration that prioritizes ethical use, prompt engineering, and critical evaluation, GenAI may compromise the cognitive autonomy of medical students. Conversely, when thoughtfully embedded into pedagogical frameworks, these tools can act as cognitive enhancers—supporting, rather than replacing, clinical reasoning. Medical education must adapt to ensure that future physicians engage with GenAI in a critical, ethical, and context-aware manner, especially in complex decision-making scenarios. This transformation demands not only technological fluency but also reflective practice and sustained oversight by faculty and academic institutions.

The NLRP3 inflammasome is a key cytosolic sensor in the innate immune system, activated by diverse danger signals such as metabolic stress, infections, and structural cellular disruptions. Its activation leads to the maturation of IL-1β and IL-18 and induces pyroptosis through gasdermin D cleavage. Multiple regulatory mechanisms modulate NLRP3 activation, including BRCC3-mediated deubiquitination, lysine carbamylation, intracellular trafficking to the microtubule-organizing center, and endolysosomal localization via PI4P. Dysregulation of these checkpoints contributes to inflammatory, neurodegenerative, hepatic, metabolic, and infectious diseases. Beyond pathogen defense, inflammasomes influence tissue regeneration, cell death pathways, and sterile inflammation, highlighting their role as integrative immune hubs. Alternative inflammatory pathways involving gasdermin E and caspase-8/3 enable persistent cytokine release in the absence of gasdermin D, revealing redundant effector arms within the inflammasome network. Structural triggers such as potassium efflux and intracellular transport disruptions lower the threshold for inflammasome assembly, while hypoxic conditions link its activation to immunometabolic imbalance. Aggresome-like mechanisms further reflect a convergence between proteostasis and inflammation. While NLRP3 remains the most extensively characterized, other inflammasomes—including NLRP1 in epithelial ribotoxic stress, CARD8 in HIV-1 protease sensing, and AIM2/IFI16 in viral and DNA sensing—highlight the diversity of inflammasome signaling in tissue- and pathogen-specific contexts. Small molecules such as MCC950, thiolutin, HDAC6 inhibitors, and CuET have demonstrated efficacy in preclinical models by selectively modulating inflammasome components or their regulatory pathways. Novel strategies such as carbamylation-mediated suppression and disruption of endocytic dynamics offer additional therapeutic entry points. A deeper understanding of inflammasome biology is essential for advancing precision immunotherapy in inflammatory and infectious diseases.

Sepsis, a medical emergency with high mortality rates, demands comprehensive care spanning from early identification to patient rehabilitation. The sepsis survival chain encompasses early recognition, severity assessment, activation of emergency services, initial antimicrobial therapy, hemodynamic stabilization, and integrated rehabilitation. These interconnected steps are critical to reducing morbidity and mortality. Despite advancements in international guidelines, adherence remains limited, contributing to a significant disease burden. Beyond its acute phase, post-sepsis syndrome (PSS) is characterized by long-term immune dysregulation, chronic inflammation, and metabolic dysfunction, predisposing survivors to recurrent infections, cardiovascular disease, and neurocognitive decline. Mitochondrial dysfunction and epigenetic modifications play a central role in prolonged immunosuppression, impairing adaptive and innate immune responses. Sepsis-induced organ dysfunction impacts multiple systems, including the brain, heart, and kidneys. In the brain, it is associated with neuroinflammation, blood-brain barrier dysfunction, and the accumulation of neurotoxic proteins, leading to acute and chronic cognitive impairment. Myocardial dysfunction involves inflammatory mediators such as TNF-α and IL-6, while sepsis-associated acute kidney injury (SA-AKI) arises from hypoperfusion and inflammation, heightening the risk of progression to chronic kidney disease. Additionally, immune alterations such as neutrophil dysfunction, continuous platelet activation, and suppressed antitumoral responses contribute to increased infection risk and long-term complications. Timely and targeted interventions, including antimicrobial therapy, cytokine modulation, immune restoration, metabolic support, and structured rehabilitation strategies, are pivotal for improving outcomes. However, financial and infrastructural limitations in low-resource settings pose significant barriers to effective sepsis management. Precision medicine, AI-driven early warning systems, and optimized referral networks can enhance early detection and personalized treatments. Promoting public and professional awareness of sepsis, strengthening multidisciplinary post-sepsis care, and integrating long-term follow-up programs are imperative priorities for reducing mortality and improving the quality of life in sepsis survivors.

Sepsis is a life-threatening syndrome characterized by a dysregulated immune response to infection, frequently leading to multiorgan failure and high mortality. Inflammasomes—cytosolic multiprotein complexes of the innate immune system—serve as critical platforms for sensing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs). Key sensors such as NLRP3, AIM2, and IFI16 initiate caspase-1 activation, IL-1β and IL-18 maturation, and gasdermin D–mediated pyroptosis. In sepsis, excessive inflammasome activation drives oxidative stress, endothelial dysfunction, immunothrombosis, and immune exhaustion. This maladaptive cascade is further aggravated by the release of DAMPs and procoagulant factors, compromising vascular integrity and immune homeostasis. Prolonged activation contributes to immunoparalysis, lymphopenia, and increased susceptibility to secondary infections. Inflammasome signaling also intersects with necroptosis and ferroptosis, amplifying systemic inflammation and tissue injury. Additionally, various pathogens exploit immune evasion strategies to modulate inflammasome responses and enhance virulence. Therapeutic interventions under investigation include selective NLRP3 inhibitors, IL-1 blockers, gasdermin D antagonists, and extracorporeal cytokine hemoadsorption. Emerging approaches emphasize biomarker-guided immunomodulation to achieve personalized therapy. While preclinical studies have shown promising results, clinical translation remains limited. Targeting inflammasomes may offer a path toward precision immunotherapy in sepsis, with potential to reduce organ dysfunction and improve survival.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from chromaffin cells, with 80–85% originating in the adrenal medulla and 15–20% from extra-adrenal chromaffin tissues (paragangliomas). Approximately 30–40% of PPGLs have a hereditary component, making them one of the most genetically predisposed tumor types. Recent advances in genetic research have classified PPGLs into three molecular clusters: pseudohypoxia-related, kinase-signaling, and WNT-signaling pathway variants. Specifically, the detection of SDHB-related tumors indicates an increased risk of metastatic disease, which may impact decisions regarding functional imaging in patients with high suspicion of metastasis and influence targeted treatment strategies. Diagnosis of PPGLs primarily relies on biochemical testing, measuring catecholamines or their metabolites in plasma or urine. However, molecular testing, functional imaging, and targeted therapies have greatly enhanced diagnostic precision and management. Personalized treatment approaches based on genetic profiling are becoming integral to the clinical management of these tumors. In South American countries like Colombia, functional imaging techniques such as positron emission tomography/computed tomography (PET/CT) with tracers like 18F-DOPA, 18F-fluorodeoxyglucose (18F-FDG), and 68Ga-DOTA-conjugated somatostatin receptor-targeting peptides (68Ga-DOTA-SST) are used to guide follow-up and treatment strategies. Radionuclide therapy with lutetium-177 DOTATATE is employed for patients showing uptake in 68Ga-DOTA-SST PET/CT scans, while access to 131-MIBG therapy remains limited due to high costs and availability. Recent clinical trials have shown promise for systemic therapies such as sunitinib and cabozantinib, offering potential new options for patients with slow or moderate progression of PPGLs. These advancements underscore the potential of personalized and targeted therapies to improve outcomes in this challenging patient population.

Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection. It follows a dynamic course in which early hyperinflammation coexists and overlaps with progressive immune suppression, a process best described as immunodynamic disruption. Key mechanisms include extensive lymphocyte death, expansion of regulatory T cells, impaired antigen presentation, and persistent activation of inhibitory checkpoints such as programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte–associated protein 4 (CTLA-4). These changes reduce immune competence and increase vulnerability to secondary infections. Clinically, reduced expression of Human Leukocyte Antigen–DR (HLA-DR) on monocytes and persistent lymphopenia have emerged as robust biomarkers for patient stratification and timing of immunomodulatory therapies. Beyond the acute phase, many survivors do not achieve full immune recovery but instead develop a Persistent Immune Remnant, defined as long-lasting immune, metabolic, and endothelial dysfunction despite apparent clinical resolution. Recognizing PIR emphasizes the need for long-term monitoring and biomarker-guided interventions to restore immune balance. To integrate these observations, we propose the SIMMP–Sepsis model (Sepsis-Associated Persistent Multiorgan Immunometabolic Syndrome), which links molecular dysfunction to clinical trajectories and provides a framework for developing precision immunotherapies. This perspective reframes sepsis not only as an acute crisis but also as a chronic immunometabolic syndrome, where survival marks the beginning of active immune restoration.