Diabetic Foot Ulcers: A Review of Debridement Techniques.

Diabetic foot ulcers (DFUs) are a prevalent complication of diabetes mellitus (DM) and lead to significant morbidity and mortality. Patients with DM have a lifetime risk of DFUs as high as 34%. The pathogenesis of DFUs is multifactorial, and the most common underlying causes are poor glycemic control, peripheral neuropathy, peripheral vascular disease, foot deformity, and poor foot care. Diabetic lower-extremity complications are also a significant burden in terms of healthcare costs. In the United States alone, the direct cost of diabetic foot care has been estimated to be $8,659 per patient, with total annual medical costs for managing diabetic foot disease ranging from $9 to $13 billion. Given the risk of amputation and poor wound healing, the fast, accurate diagnosis and treatment of DFUs are critical. Measures to prevent DFUs include glycemic control and annual foot inspections. For patients with DFUs, off-loading and local wound care are critical for wound healing. Debridement is the standard of care for DFU wounds, and several techniques exist. In this review, we discuss the current practices of diabetic wound care, different methods of debridement and their practical use in DFUs, and novel debridement approaches with the potential for improving wound-healing outcomes.

Pan-cancer Genomic Analysis of AXL Mutations Reveals a Novel, Recurrent, Functionally Activating AXL W451C Alteration Specific to Myxofibrosarcoma.

Myxofibrosarcoma (MFS) is a common soft tissue sarcoma of the elderly that typically shows low tumor mutational burden, with mutations in TP53 and in genes associated with cell cycle checkpoints ( RB1 , CDKN2A ). Unfortunately, no alterations or markers specific to MFS have been identified and, as a consequence, there are no effective targeted therapies. The receptor tyrosine kinase AXL, which drives cellular proliferation, is targetable by new antibody-based therapeutics. Expression of AXL messenger RNA is elevated in a variety of sarcoma types, with the highest levels reported in MFS, but the pathogenic significance of this finding remains unknown. To assess a role for AXL abnormalities in MFS, we undertook a search for AXL genomic alterations in a comprehensive genomic profiling database of 463,546 unique tumors (including 19,879 sarcomas, of which 315 were MFS) interrogated by targeted next-generation DNA and/or RNA sequencing. Notably, the only genomic alterations recurrent in a specific sarcoma subtype were AXL W451C (n = 8) and AXL W450C (n = 2) mutations. The tumors involved predominantly older adults (age: 44 to 81 [median: 72] y) and histologically showed epithelioid and spindle-shaped cells in a variably myxoid stroma, with 6 cases diagnosed as MFS, 3 as undifferentiated pleomorphic sarcoma (UPS), and 1 as low-grade sarcoma. The AXL W451C mutation was not identified in any non-sarcoma malignancy. A review of publicly available data sets revealed a single AXL W451C-mutant case of UPS that clustered with MFS/UPS by methylation profiling. Functional studies revealed a novel activation mechanism: the W451C mutation causes abnormal unregulated dimerization of the AXL receptor tyrosine kinase through disulfide bond formation between pairs of mutant proteins expressing ectopic cysteine residues. This dimerization triggers AXL autophosphorylation and activation of downstream ERK signaling. We further report sarcomas of diverse histologic subtypes with AXL gene amplifications, with the highest frequency of amplification identified in MFS cases without the W451C mutation. In summary, the activating AXL W451C mutation appears highly specific to MFS, with a novel mechanism to drive unregulated signaling. Moreover, AXL gene amplifications and messenger RNA overexpression are far more frequent in MFS than in other sarcoma subtypes. We conclude that these aberrations in AXL are distinct features of MFS and may aid diagnosis, as well as the selection of available targeted therapies.

Wendigo Psychosis and Psychiatric Perspectives of Cannibalism: A Complex Interplay of Culture, Psychology, and History.

Our review paper delves into the intricate and multifaceted realm of cannibalism, with a focused exploration of its manifestations in Wendigo psychosis. We aim to explore the implications of cannibalism within the realms of psychiatry, anthropology, psychology, and sociology by navigating the complexities of cultural beliefs, psychological underpinnings, historical contexts, and contemporary significance surrounding cannibalism. Cannibalism is deeply ingrained in the cultural and mythological heritage of Algonquian-speaking tribes; it is closely associated with the symbolic figure of the Wendigo. The Wendigo serves as a warning about the potential loss of one's humanity in dire circumstances like starvation. Wendigo psychosis, characterized by psychiatric manifestations such as paranoia, anxiety, hallucinations, and cannibalistic urges, often emerges as a result of a fusion of cultural narratives and psychological vulnerabilities. This may provide an outlet for individuals experiencing internal distress. Historical records show that instances of Wendigo psychosis and cannibalism were more prevalent during periods of extreme scarcity and famine among Algonquian tribes, but they can also manifest in non-famine contexts. Cannibalism assumes diverse forms and meanings across various cultures, encompassing ritualistic, sacrificial, or survival cannibalism. Acknowledging these nuances is paramount to avoiding perpetuating harmful stereotypes and to appreciating the significance of these practices within specific cultures. Engaging in discussions about cannibalism necessitates cultural sensitivity and respect for diverse cultural practices and beliefs to foster open dialogue and enhance cross-cultural understanding. Although cannibalism is often associated with psychiatric disorders, it is not exclusively rooted in mental illness. Factors like substance abuse, antisocial traits, and environmental upbringing can also contribute to cannibalistic acts. In some cases, cannibalism may be linked to survival instincts stemming from trauma and abuse. Therefore, it is vital to distinguish between various forms of cannibalism and understand their underlying motivations. Analyzing cannibalistic fantasies from a psychoanalytic perspective involves exploring mechanisms such as melancholia and oral fixation, shedding light on the psychological underpinnings of these thoughts and urges. Moreover, the influence of media portrayals of cannibalism on public perceptions cannot be underestimated. Sensationalism and romanticization in popular culture can distort our understanding of the motivations and mental states of individuals involved in cannibalistic acts. In essence, cannibalism remains an intriguing and multidimensional topic deeply entrenched in cultural narratives and psychological complexities. A comprehensive understanding necessitates a multidisciplinary approach, taking into account how historical context, cultural beliefs, psychological experiences, and societal dimensions shape human behavior and our comprehension of the human condition. To navigate this complex subject with sensitivity and respect, it is essential to recognize the diverse manifestations and motivations behind cannibalistic behavior, whether in the context of Wendigo psychosis or other cultural practices.