Chronic pain, defined by persistent pain beyond normal healing time, is a pervasive and debilitating condition affecting up to 30–50% of adults globally. In parallel, neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and cognitive or motor decline, often underpinned by pathological protein misfolding and aggregation. Emerging evidence suggests a potential mechanistic link between chronic pain and NDs, with persistent pain contributing to neuroinflammatory states and protein homeostasis disturbances that mirror processes in neurodegeneration. This review explores the hypothesis that protein misfolding and aggregation serve as a mechanistic bridge between chronic pain and neurodegeneration. We systematically examine molecular pathways of protein misfolding, proteostasis dysfunction in chronic pain, and shared neuroimmune mechanisms, highlighting prion-like propagation of misfolded proteins, chronic neuroinflammation, and oxidative stress as common denominators. We further discuss evidence from experimental models and clinical studies linking chronic pain to accelerated neurodegenerative pathology—including tau accumulation, amyloid dysregulation, and microglial activation—and consider how these insights open avenues for novel therapeutics. Targeting protein aggregation, enhancing chaperone function, modulating the unfolded protein response (UPR), and attenuating glial activation are explored as potential strategies to mitigate chronic pain and possibly slow neurodegeneration. Understanding this intersection not only elucidates chronic pain’s role in cognitive decline but also suggests that interventions addressing proteostasis and inflammation could yield dual benefits in pain management and neurodegenerative disease modification.

Chronic pain is a highly prevalent and disabling condition with a well-documented female predominance in incidence, severity and persistence. These sex differences are driven by sexually dimorphic neuroimmune mechanisms rather than psychosocial factors alone. This systematic review was conducted to comprehensively synthesize human clinical and translational evidence on sex-specific neuroimmune and glial cell pathways underlying chronic pain. Scientific literature was systematically searched from database inception to December 2025 across multiple biomedical databases to identify relevant clinical and translational studies. Across pain conditions, convergent evidence demonstrated that chronic pain mechanisms diverge by sex at cellular and molecular levels. Male-predominant pathways were characterized by microglial activation, particularly P2X4 receptor–mediated signaling and brain-derived neurotrophic factor–dependent neuronal disinhibition, supported by neuroimaging, transcriptomic, and pharmacological data. In contrast, female-predominant mechanisms involved adaptive immune processes, including CD4⁺ and CD8⁺ T cell infiltration, pannexin-1–dependent leptin release, chemokine signaling, and astrocyte-mediated neuroimmune crosstalk. Sex-specific cytokine and chemokine profiles, differential glial activation patterns, and divergent neuroimmune–endocrine interactions further distinguished pain pathways between males and females. Despite consistent mechanistic trends, substantial heterogeneity within each sex, limited sex-stratified power in many studies, and variability in outcome measures constrained quantitative synthesis and generalizability. The findings indicate that chronic pain is not a unitary disorder but rather a collection of mechanistically distinct conditions shaped by biological sex. These results highlight the limitations of sex-neutral therapeutic strategies and support the development of precision medicine approaches incorporating sex-informed neuroimmune biomarkers and mechanism-matched interventions. Future studies should prioritize adequately powered sex-stratified analyses, integration of neuroimmune biomarkers and clinical trial designs capable of detecting sex-by-treatment interactions.

Background: Cytokine release syndrome (CRS) is a life-threatening systemic inflammatory condition marked by excessive cytokine production, leading to multi-organ dysfunction. It is commonly associated with T-cell-engaging therapies such as chimeric antigen receptor (CAR) T cells, T-cell receptor bispecific molecules, and monoclonal antibodies. Carfilzomib, a proteasome inhibitor, is known to cause a range of adverse effects, primarily hematologic and cardiovascular. However, multiorgan failure grade 5 (fatal), resembling CRS has not been previously reported in association with Carfilzomib. Case Report: A 74-year-old male with relapsed multiple myeloma developed grade 5 multiorgan failure 60 min after the third dose of Carfilzomib, resulting in death within 24 h of symptom onset. The patient tolerated the first doses of Carfilzomib well with only fever and headache developing post infusion. Before the second dose, the patient developed worsening pancytopenia, prompting the discontinuation of Lenalidomide. After the second Carfilzomib infusion, he experienced fever and transient encephalopathy, which resolved with acetaminophen, corticosteroids, and supportive care. However, following the third dose, he rapidly deteriorated—developing fever, tachycardia, hypotension, hypoxia, and encephalopathy. Despite aggressive management with intravenous fluids, broad-spectrum antibiotics, corticosteroids, and tocilizumab, the patient progressed to refractory shock and multi-organ failure, culminating in death within 24 h. A comprehensive infectious workup was negative, ruling out sepsis and suggesting possible Carfilzomib-induced CRS. Conclusion: Grade 5 multiorgan failure with signs and symptoms similar with CRS following Carfilzomib administration is a rare but potentially fatal adverse drug reaction. Further research is needed to better define the risk factors and optimal management strategies for Carfilzomib-induced multiorgan failure and possible CRS.

This review aims to explore the use and educational impact of the Pecha Kucha presentation format in medical education, as well as its integration with active learning methodologies. A comprehensive literature search was conducted in Medline, Embase, ScienceDirect, and Scopus to identify studies that assessed Pecha Kucha in undergraduate, postgraduate, or patient education. Fourteen English-language studies published up to September 2024 were included. Studies were evaluated for design, participant population, learning outcomes, and pedagogical integration. The selected studies employed quantitative, qualitative, and mixed-method approaches. Most studies reported positive educational outcomes, including improved knowledge retention, clearer communication, and enhanced learner engagement. Pecha Kucha was particularly effective when integrated with self-directed, problem-based, case-based, or team-based learning strategies. Participants, including students, residents, and patients, highlighted the format’s value in promoting concise, visually engaging presentations, although some noted difficulties adapting to its strict timing constraints. Pecha Kucha is a promising educational tool that incites active learning, efficient communication, and engagement in medical education. When combined with other pedagogical strategies, it contributes to a more dynamic and student-centered learning environment.

IntroductionChronic pain presents a multifaceted challenge in clinical practice, necessitating a nuanced understanding of pharmacological interventions to optimize treatment outcomes. This review provides an outline of various pharmacological agents commonly used in chronic pain management and highlights their safety considerations, particularly regarding suicide risk.Areas coveredThis review discusses the role of antidepressants, anticonvulsants, GABA receptor agonists, NMDA receptor antagonists, corticosteroids, cannabis and cannabinoids, bisphosphonates, calcitonin, and alpha-2 adrenergic receptor agonists in chronic pain management. It assesses their therapeutic benefits, potential for misuse, and psychiatric adverse effects, including the risk of suicide. Each pharmacological class is evaluated in terms of its efficacy, safety profile, and considerations for clinical practice. We searched peer-reviewed English literature on the topic using the MEDLINE database without time restrictions.Expert opinionWhile pharmacological interventions offer promise in alleviating chronic pain, healthcare providers must carefully weigh their benefits against potential risks, including the risk of exacerbating psychiatric symptoms and increasing suicide risk. Individualized treatment approaches, close monitoring, and multidisciplinary collaboration are essential for optimizing pain management strategies while mitigating adverse effects. Ongoing research efforts are crucial for advancing our understanding of these pharmacological interventions and refining pain management practices.

Fat embolism syndrome (FES) is a rare but serious complication most commonly associated with trauma, particularly long bone fractures. However, symptomatic FES remains a significant diagnostic and therapeutic challenge. We present the case of a 20-year-old man who, after sustaining multiple long bone fractures in a motorcycle accident and initially appearing stable, experienced a rapid and fatal progression of FES. This case underscores the unpredictable course of FES even in young, previously healthy individuals and highlights the critical need for early recognition and intervention. It also emphasizes the importance of identifying risk factors that may predict severe outcomes and mortality.