Multisystem inflammatory syndrome in children (MIS-C) is an emergent postinfectious hyperinflammatory disorder predominantly affecting the pediatric population following COVID-19 infection. Clinically, it is characterized by persistent fever, shock, multiorgan involvement, and potentially severe cardiovascular involvement. This comprehensive review synthesizes current evidence on the epidemiology, pathophysiology, clinical presentation, diagnostic criteria, with particular emphasis on the management of MIS-C. We also stress on the importance of distinguishing MIS-C from phenotypically similar entities. Acute-phase management centers on supportive care, hemodynamic stabilization, and targeted immunomodulation, with intravenous immunoglobulin, corticosteroids, and biologic forming the therapeutic cornerstone. Thromboprophylaxis is frequently warranted due to the elevated thromboembolic risk, and long-term follow-up is essential to monitor for cardiac, gastrointestinal, and neurologic complications. Additional considerations include postrecovery vaccination protocols and the use of extracorporeal membrane oxygenation in cases of refractory cardiorespiratory failure. Despite advancements in clinical outcomes, diagnostic ambiguity and heterogeneous management guidelines continue to pose significant challenges.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare and distinct histologic subtype of hepatocellular carcinoma that typically arises in non-cirrhotic livers of adolescents and young adults without underlying viral hepatitis or chronic liver disease. Accounting for less than 1% of all primary liver cancers, FLC is characterized by unique clinical, radiologic, and molecular features, most notably the highly characteristic DNAJB1–PRKACA fusion. Due to its rarity and frequently nonspecific presentation, diagnosis is often delayed or misinterpreted as by benign hepatic lesions such as focal nodular hyperplasia or adenoma. This report presents a rare case of metastatic FLC in a young adult who initially presented with right upper quadrant pain, anemia, and preserved hepatic function. Imaging revealed a large hepatic mass with a central non-enhancing area suggestive of necrosis, and histopathologic evaluation aided in the diagnosis based on characteristic lamellar fibrosis, polygonal eosinophilic cells, and positive CK7 and HepPar-1 staining. Confirmatory molecular testing through DNAJB1–PRKACA fusion was not performed. Planned treatment with a combination regimen of nivolumab and neratinib was scheduled; however, the patient deteriorated rapidly, and systemic therapy could not be initiated before death. Through this case and accompanying review, we aim to highlight the diagnostic complexity, molecular underpinnings, and current therapeutic approaches of FLC. This case was notable for advanced peritoneal carcinomatosis at presentation, severe thrombocytosis, and the diagnostic and therapeutic challenges posed by metastatic fibrolamellar carcinoma without molecular confirmation. Taken together, this underscores the importance of early recognition, molecular testing, and coordinated clinical management in optimizing outcomes for this uncommon malignancy.

Cutaneous melanoma remains a global health challenge. Although BRAF/MEK-targeted therapies and immune checkpoint inhibitors (ICIs) have improved outcomes in advanced disease, durable responses remain difficult to achieve for most patients. Therapeutic resistance represents the central barrier to long-term disease control. This review comprehensively examines the molecular and immunologic mechanisms underlying melanoma resistance and integrates these insights with emerging pharmaceutical strategies designed to overcome them. We explore the genetic landscape of melanoma, including oncogenic alterations in BRAF, NRAS, NF1, CDKN2A, and PTEN, and explain how dysregulation of the MAPK and PI3K/AKT/mTOR signaling axes drives therapeutic escape. Phenotypic plasticity is discussed as a critical epigenetic driver of drug tolerance. The tumor microenvironment (TME) is examined as an active co-conspirator in resistance, encompassing immunosuppressive cell populations, cancer-associated fibroblasts, and metabolic competition. Resistance mechanisms to targeted therapy, including MAPK reactivation, bypass signaling, transcriptional reprogramming, and metabolic rewiring, are reviewed alongside tumor-intrinsic and tumor-extrinsic mechanisms of ICI resistance. Emerging therapeutic strategies are surveyed, including next-generation RAF and ERK inhibitors, dual-pathway blockade, and metabolic therapies targeting oxidative phosphorylation. Innovations in molecular imaging, liquid biopsy, and artificial intelligence-driven biomarker discovery are highlighted as pivotal tools for real-time resistance monitoring and adaptive treatment. By linking mechanistic insights with translational advances, this review advocates for combination strategies and adaptive clinical frameworks to achieve more durable disease control in melanoma.

Vascular smooth muscle cells (VSMCs) play a central role in maintaining vascular tone, structural integrity, and adaptive remodeling. With aging and chronic cardiometabolic stress, however, VSMCs undergo senescence driven by telomere attrition, oxidative stress, persistent DNA-damage signaling, and dysregulation of the p53/p21 and p16/Rb pathways. This transition is accompanied by acquisition of a senescence-associated secretory phenotype (SASP), which promotes inflammation, extracellular matrix remodeling, calcification and vascular stiffening. Together, these accelerate atherosclerosis, hypertension, aneurysm formation, and related vasculopathies. Growing evidence identifies VSMC senescence as a promising therapeutic entry point for cardiovascular drug discovery. Emerging strategies include senolytics, senomorphics, metabolic modulators, and molecular reprogramming approaches designed to either eliminate senescent cells or attenuate their pathogenic secretome and downstream signaling networks. In this review, the molecular basis of VSMC senescence, its contribution to major vascular disorders, and the therapeutic landscape targeting senescence-associated pathways are discussed, with emphasis on translational opportunities and current barriers to clinical application. A clearer understanding of VSMC senescence may inform the development of mechanism-based interventions to limit vascular dysfunction and age-related cardiovascular disease.