Search results for: neoadjuvant therapy

Authors: Jenny Carpenter, Josh Chan, Persephone MacKinlay, Madeline Chiang, Devlyn Sun, Hiba Syed, Jana Lau, Mariam Arshad, Joy Xu

Abstract:

Introduction: Psoriasis is a chronic inflammatory skin condition that affects 1 million Canadians and over 8 million Americans. It is associated with psychosocial challenges exacerbated by the presence of visible lesions, which can lead to feelings of embarrassment and social discomfort. Children often experience bullying and lower self-esteem, while adults face workplace discrimination, impaired productivity, and higher rates of comorbid mental health conditions. Understanding these impacts across age groups is vital for tailored interventions. Objective: The main objective is to compare the longitudinal psychological impact of psoriasis between adults and children in Canada and the United States. Methods: This systematic review was conducted following PRISMA guidelines and a PROSPERO-registered protocol. Studies were identified from PubMed, Scopus, ProQuest, PsycINFO, Dermatology Online Journal, JMIR Dermatology, and Embase. The included studies were published between 2014 and 2024, measured standardized psychological outcomes, and had a longitudinal design with at least a one-year follow-up period. Methodological quality was assessed using the GRADE tool. Results: Fifteen studies encompassing 67,964 participants (mean age 49.1 years, 53.3% female) were included. Adults with moderate-to-severe psoriasis demonstrated significant impairments in Dermatology Life Quality Index (DLQI) scores, with a mean baseline score of 9.0 to 10.2 for severe cases, reflecting moderate-to-severe quality of life (QoL) impairments. Treatment with biologic therapies significantly improved outcomes, with DLQI scores decreasing by an average of 7 points (from 9.6 to 2.6; p < 0.001). Key areas of improvement included social functioning, reduced physical symptoms, and increased work productivity. In severe cases, DLQI scores were 7.95 points higher compared to mild cases (p < 0.05), indicating a disproportionate burden of disease severity. Anxiety and depression were common in adults, affecting 16-23% and 18-22%, respectively. These conditions were linked to visible lesions, social stigma, and comorbidities such as hypertension and metabolic syndrome. Children with psoriasis also exhibited similar impairments in QoL, as assessed by the Children’s Life Quality Index (CLDQI). Visible lesions negatively affected school participation and peer interactions, with bullying and stigma consistently reported as major contributors to social isolation and emotional distress. Although biological therapies improved CDLQI scores, children faced persistent challenges in psychological well-being, including lower self-esteem and stigma, which often persisted in adolescence. Disease severity was quantified using the Psoriasis Area and Severity Index (PASI). Among adults, severe cases had a mean baseline PASI score of 13.9, improving by 87.1% (to 1.8, p < 0001) following biologic therapy. Canadian cohorts showed greater PASI improvements, with biologic-naive adults achieving a 95.1% reduction (from 16.3 to 0.7, p < 0.0001). Canadian patients also had higher biologic continuation rates (89.9%). Conclusion: Psoriasis significantly impacts quality of life and psychological well-being across age groups, with notable differences in outcomes between adults and children. Regional differences further highlighted greater work-related impairments in U.S. adults and more pronounced psychological challenges in Canadian children, where bullying and stigma delayed recovery. These findings emphasize the need for age- and region-specific strategies to address both the physical and psychosocial dimensions of psoriasis and support long-term well-being.

Keywords: psoriasis, psychological impact, mental health, quality of life, self-esteem, autoimmune, chronic skin condition

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Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

Procedia PDF Downloads 80

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

Procedia PDF Downloads 88