Search

Introduction: Pemphigus vulgaris (PV) is a rare intraepidermal blistering disease that is potentially life-threatening due to risk of infection and failure of skin barrier function. The identification of biomarkers has the potential to provide diagnostic utility and identify new therapeutic targets. The objective of this systematic review is to identify all potentially relevant PV biomarkers, categorize them, and identify trends to determine the involvement of T-cell-mediated, B-cell-1mediated, and innate immune-mediated pathways in PV pathogenesis. Methods/Results: Medline and Embase databases were searched according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, resulting in the inclusion of 66 studies that reported on a total of 2463 patients and 146 unique biomarkers. Biomarkers were categorized into T-cell-mediated, B-cell-mediated, and innate immune system pathways. The most notable biomarkers trends include elevations in IL-4, IL-6, IL-17A, anti-Dsg1/3 autoantibodies, and a reduction in Treg cells and FOXP3. Conclusion: The results of this review support current theories of PV pathogenesis, with increased Th2 activity, increased Th17 activity, decreased Treg activity, and production of anti-Dsg1/3 autoantibodies being observed. Targeting of IL-4 and IL-6 may provide therapeutic benefit. However, more research is required to validate biomarkers for clinical utility and assess viability as therapeutic targets. [ABSTRACT FROM AUTHOR]

Introduction: Rosacea is a chronic inflammatory skin condition affecting approximately 5.5% of the global population. Patients present heterogeneously with a mix of features in the central facial region, of which papules and pustules are considered to be a major feature. The identification of effective treatments for reducing inflammatory lesions in rosacea can alleviate the psychosocial burden that many rosacea patients experience, including reduced self-esteem, anxiety, and social withdrawal. The objective of this systematic review is to determine the effectiveness of topical and systemic therapies in reducing lesion count in rosacea patients. Methods/Results: Medline, Embase, and Cochrane CENTRAL databases were searched, resulting in the inclusion of 43 clinical trials reporting on a total of 18,347 rosacea patients. The most well-studied treatments include ivermectin, metronidazole, azelaic acid, minocycline, and doxycycline. Oral isotretinoin was the most effective treatment in reducing inflammatory lesions and may be recommended for severe recalcitrant cases of rosacea. Conclusions: Several topical and systemic therapies have demonstrated efficacy in reducing inflammatory lesion count in rosacea patients, with mechanisms of action centred around suppressing inflammation and killing Demodex folliculorum mites. Additional research is required to determine effective combination therapies in rosacea. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal for the Scholarship of Teaching & Learning is the property of Society for Teaching & Learning in Higher Education and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article "Bimatoprost for the management of vitiligo: A systematic review and meta-analysis" explores the use of bimatoprost, a prostaglandin F2-alpha analogue, for treating vitiligo. The study reviewed evidence on bimatoprost's effectiveness and safety for vitiligo treatment, analyzing outcomes such as clinical repigmentation, vitiligo surface area, and patient satisfaction. Results showed promising outcomes, especially when bimatoprost was used in combination with other therapies like NB-UVB phototherapy and FxCO2 laser. The study acknowledges limitations such as small sample sizes and varied protocols, emphasizing the need for further research to understand the long-term efficacy of bimatoprost for vitiligo treatment. [Extracted from the article]

Introduction While clinical trial data demonstrates the efficacy and safety of upadacitinib (UPA), an oral Janus kinase inhibitor (JAKi) for atopic dermatitis (AD), long-term real-world evidence remains limited. Objectives Our study evaluated the real-world effectiveness and safety of UPA for AD at week 52±6. Methods We conducted a multicenter retrospective review of 3 practices in Canada. Effectiveness endpoints were evaluated at weeks 52±6 and including the following: Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) as well as improvements in Eczema Area and Severity Index (EASI), body surface area (BSA), IGAxBSA, and Dermatology Life Quality Index (DLQI)/Children's DLQI (CDLQI). Safety was determined via incidence of treatment-related adverse events (AEs). Results A total of 102 patients with AD were included in the analysis; mean age was 44.2 (range: 12-79) years and 52.9% (54/102) were female. Initial UPA doses were 15 mg (UPA15: 41.2%, 42/102) or 30 mg (UPA30: 58.8%, 60/102) once daily. Previous systemic therapies included conventional non-biologics (72.5%), biologics (30.4%), and JAKi (2.9%). At week 52±6: 78.4% (80/102) of patients achieved Investigator Global Assessment (IGA) 0/1; 87.5% (49/56), 78.6% (44/56), and 50.0% (28/56) achieved Eczema Area and Severity Index (EASI) improvements of 75% (EASI75), 90% (EASI90), and 100% (EASI100), respectively; 75.0% (42/56) achieved EASI90 + IGA 0/1; mean EASI was reduced from 12.9 to 0.8 (mean EASI improvement = 91.4%); 91.9% (52/56), 92.9% (52/56), 82.1% (46/56), and 75.0% (42/56) achieved absolute EASI scores < 7, < 5, < 3, and < 1, respectively; mean body surface area (BSA) was reduced from 17.0% to 0.6% (mean BSA improvement=87.8%); mean IGAxBSA was reduced from 52.1 to 0.8 (mean IGAxBSA improvement=90.7%); and mean Dermatology Life Quality Index (DLQI)/Children's DLQI was reduced from 13 to 1.8 (mean DLQI/CDLQI improvement=86%), with 66.0% (33/50) of patients achieving DLQI/CDLQI 0/1. For patients not achieving IGA 0/1, EASI75, EASI90, and EASI100 at weeks 8-20, these responses were subsequently achieved in 60.0% (6/10), 88.9% (8/9), 84.6% (11/13), and 38.1% (8/21) of patients at week 52±6. Dose alterations occurred in 13 patients (12.7%) (escalation: 6.9%, 7/102; reduction: 5.9%, 6/102). Concomitant systemic therapies were used in 1.0% (1/102) of patients. We noted higher statistically significant achievement of endpoints for systemic biologic/JAKi-naïve vs -experienced patients (EASI75; EASI < 7; EASI < 5; DLQI/CDLQI > 4-point improvement). No significant differences in outcomes were identified between dosing regimens. Frequent AEs included: acne (19.6%, 20/102), hypertriglyceridemia (17.6%, 18/102), elevated creatine phosphokinase (13.7%, 14/102), neutropenia (7.8%, 8/102), and transaminitis (7.8%, 8/102). Seven patients (6.8%) discontinued UPA owing to treatment-related AEs, including one case of venous thromboembolism; four patients (3.9%) discontinued UPA due to patient preference, and one patient (1%) discontinued UPA due to lack of efficacy. No serious infections, tuberculosis, major adverse cardiovascular events, gastrointestinal perforation, malignancy, or deaths were observed in 102.5 patient-years of follow-up. Conclusions In contrast to 52-week data from the Measure Up 1/2 and AD Up clinical trials, our results were superior for several outcome parameters (IGA 0/1, EASI90, EASI100, and DLQI 0/1), possibly owing to a patient population with less extensive baseline disease severity. Additionally, we noted similar achievement of these endpoints versus comparable long-term real-world studies. Safety was consistent with existing data, highlighting acne as a common AE (5.3%-20.3% versus 19.6%). Study limitations include its sample size and retrospective nature. [ABSTRACT FROM AUTHOR]

Introduction Upadacitinib (UPA), an oral, selective Janus kinase inhibitor (JAKi), is approved for moderate-to-severe atopic dermatitis (AD). While its efficacy and safety are supported by clinical trial data1-3, real-world evidence is limited. Objectives Our study evaluated the real-world effectiveness and safety of UPA for AD between weeks 8-20. Methods We conducted a multicenter retrospective review at three practices in Canada. Effectiveness endpoints measured between weeks 8-20 included: Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) and improvements in Eczema Area and Severity Index (EASI), body surface area (BSA), IGAxBSA, and Dermatology Life Quality Index (DLQI)/Children's DLQI (CDLQI) improvements. Safety was assessed via treatment-related adverse events (AEs). Results A total of 179 patients were included in the analysis.. The mean age was 44.6 ± 17.5 (range: 12-79) years; 53.6% (96/179) were female. Previous treatments included: topicals (100%, 179/179), light (29.1%, 52/179), systemic non-biologics (74.9%, 134/179), and systemic biologics/JAKi (37.4%, 67/179). Initial UPA doses were 15 mg (44.7%, 80/179) or 30 mg (55.3%, 99/179) once daily. At weeks 8-20: 87.2% (156/179) of patients achieved IGA 0/1; 83.3% (85/102), 74.5% (76/102), and 57.8% (59/102) of patients achieved EASI improvements from baseline of 75% (EASI75), 90% (EASI90), and 100% (EASI100), respectively; mean EASI was reduced from 13.4 to 1.0 (p=0.0001; mean EASI improvement = 88.5%); 98% (100/102), 96.1% (98/102), 88.2% (90/102), and 70.6% (72/102) of patients achieved absolute EASI scores < 7, < 5, < 3, and < 1, respectively; mean BSA was reduced from 18.2% to 1.1% (p=0.0001; mean BSA improvement=92.2%); mean IGAxBSA was reduced from 60.9 to 2.1 (p=0.0001; mean IGAxBSA improvement=94.7%); and mean DLQI/CDLQI was reduced from 13.6 to 1.4 (p=0.0001; mean DLQI/CDLQI improvement=87.1%), with 75.9% (63/83) of patients achieving DLQI/CDLQI 0/1. UPA monotherapy was utilized in 39.7% (71/179) of cases. Common concomitant therapies included topical corticosteroids (55.3%, 99/179), topical calcineurin inhibitors (6.7%, 12/179), and intramuscular triamcinolone acetonide (2.2%, 4/179). Statistically significantly higher achievement of endpoints was noted for patients using concomitant therapies (EASI75; EASI90; EASI < 1) and systemic biologic/JAKi-naïve patients (EASI75; EASI < 5; IGA 0/1; DLQI/CDLQI > 4-point improvement). Outcomes were not significantly different between dosing regimens. Frequent AEs included: acne (16.2%, 29/179), hypertriglyceridemia (14%, 25/179), elevated creatinine phosphokinase (10.1%, 18/179), herpes simplex virus (6.7%, 12/179), and transaminitis (4.5%, 8/179). Three patients (1.7%) discontinued treatment (myalgia/arthralgia [n=2]; gastrointestinal discomfort [n=1]). No serious infections, tuberculosis, venous thromboembolism, major adverse cardiovascular events, gastrointestinal perforation, or malignancy were observed in 44.7 patient-years of safety follow-up for the treatment period being analyzed. Conclusions Our study included 75.4% (135/179) of patients with follow-up at weeks ≥12 to ≤16. Interestingly, we found more favourable results than Measure Up 1/2 and AD Up clinical trials at week 16 for IGA 0/1, EASI75, EASI90, EASI100, and DLQI 0/1, likely owing to a patient population with less extensive baseline disease severity, while the safety profile was commensurate. Additionally, we noted higher achievement of IGA 0/1, EASI75, and EASI90 endpoints versus similar real-world studies. Study limitations include its retrospective nature and short follow-up duration. Nonetheless, our results support clinical trial findings suggesting UPA is effective and safe for AD. [ABSTRACT FROM AUTHOR]

Introduction Currently approved dosing regimens of upadacitinib (UPA) for moderate-to-severe atopic dermatitis (AD) are 15 mg (UPA15) once daily (QD) and 30 mg (UPA30) QD based on clinical trial data. However, dose alterations may be required in the context of inadequate efficacy, adverse events (AEs), and patient preference. Objectives Our multicenter retrospective study evaluated the effect of upadacitinib dose alterations on real-world effectiveness and safety outcomes in patients with AD at three practices in Canada. Methods Among 119 patients with AD initiated on UPA with > 23-week follow-up, we identified patients undergoing dose alteration (escalation or reduction). Reasons for dose alteration were collected along with effects of dose alteration on effectiveness outcomes including Investigator Global Assessment (IGA), mean Eczema Area and Severity Index (EASI), body surface area (BSA), Dermatology Life Quality Index (DLQI)/Children's DLQI (CDLQI), and IGAxBSA. Impact of dose alteration on incidence and outcomes of AEs was additionally analyzed. Results From 119 total patients with AD initiated on UPA (> 23-week follow-up), 26.9% (32/119) underwent dose alteration: 40.6% (13/32) with dose escalation and 59.4% (19/32) with dose reduction. The mean age of patients who underwent dose alteration was 44.8 (range: 12-79) years; 62.5% (20/32) were female and 15.6% (5/32) were adolescents. Initial doses were UPA15 (43.8%, 14/32) and UPA30 (56.3%, 18/32). The mean time from UPA initiation to dose alteration was 228.3 (range: 9-520) days. Thirteen patients underwent dose escalation: 69.2% (9/13) from UPA15 QD to UPA30 QD and 30.8% (4/13) from UPA30 QD to 45 mg (UPA45) QD. At the time of dose escalation: mean EASI score was 2.8 (mean EASI improvement from baseline: 57.4%), with 53.8% (7/13) and 7.7% (1/13) having achieved 75% and 90% improvements in baseline EASI scores (EASI75 and EASI90), respectively, while IGA scores were 1 (n=5) and 2 (n=8). At follow-up (mean duration: 83.3 days) after dose escalation: mean EASI score was 1.6 (mean EASI improvement: 84.4% [from baseline] and 54% [from date of dose escalation]), with 69.2% (9/13), 61.5% (8/13), 38.5% (5/13), and 61.5% (8/13) of patients achieving EASI75, EASI90, 100% improvement in EASI (EASI100), and IGA 0/1, respectively. Two patients (15.4%) discontinued UPA due to lack of efficacy despite dose escalation. Only 2 AEs were noted with dose escalation: transaminitis (n=1) and elevated creatine phosphokinase (n=1); the patient with transaminitis subsequently discontinued UPA. Nineteen patients underwent dose reduction: UPA30 QD to UPA15 QD (63.1%, 12/19), UPA30 QD to UPA30 every other day (QOD) (10.5%, 2/19), and UPA15 QD to UPA15 QOD (26.3%, 7/19). Reasons for dose reduction included AEs (57.9%, 11/19) and patient preference following clearance or near-clearance (42.1%, 8/19). EASI/IGA responses were maintained in 78.9% (15/19) patients. Following dose reduction, 21.1% (4/19) of patients flared and required re-escalation (mean duration: 147.3 days). AEs requiring dose reduction included acne (36.4%, 4/11), herpes simplex (18.2%, 2/11), transaminitis (18.2%, 2/11), folliculitis (9.1%, 1/11), and recurrent respiratory tract infections (18.2%, 2/11). AEs improved in 54.5% (6/11) patients with dose reduction (mean follow-up: 164.1 days). Conclusions Our real-world data suggests dose escalation from UPA15 to UPA30 and UPA30 to UPA45 (off-label) can result in higher skin clearance without any short-term safety concerns. Comparable to a Japanese real-world study (n=23), we noted incremental benefits with dose escalation, including comparable and superior achievement of EASI75 (69.2% vs. 66.7%) and EASI90 (61.5% vs. 38.1%), respectively. Furthermore, we identified AEs at higher UPA doses can improve through dose reduction with majority of patients (78.9%) maintaining initial effectiveness response. Study limitations include its small sample size and retrospective nature. [ABSTRACT FROM AUTHOR]

Introduction While clinical trial data demonstrates the efficacy and safety of upadacitinib (UPA), a selective oral Janus kinase inhibitor (JAKi) for atopic dermatitis (AD), there is still a lack of real-world evidence. Objectives Our study evaluated the real-world effectiveness and safety of UPA for AD at weeks 20-32. Methods We conducted a multicenter retrospective review at three practices in Canada. Effectiveness endpoints evaluated at weeks 20-32 included Investigator Global Assessment (IGA) score of clear or almost clear (IGA 0/1) as well as improvements in Eczema Area and Severity Index (EASI), body surface area (BSA), IGAxBSA, and Dermatology Life Quality Index (DLQI)/Children's DLQI (CDLQI). Safety was -determined via incidence of treatment-related adverse events (AEs). Results A total of 131 patients were included in the analysis. Mean age was 44.3 ± 17.5 (range: 12-78) years; 53.4% (70/131) were female. UPA doses were 15 mg (43.5%, 57/131) or 30 mg (56.5%, 74/131) once daily. Previous treatments included: topical therapy (100%, 131/131), phototherapy (29%, 38/131), systemic non-biologic therapy (75.6%, 99/131), and systemic biologic/JAKi therapy (38.9%, 51/131). At weeks 20-32: 85.5% (112/131) of patients achieved IGA 0/1; 84.3% (59/70), 75.7% (53/70), and 62.9% (44/70) of patients achieved EASI improvements of 75% (EASI75), 90% (EASI90), and 100% (EASI100), respectively; mean EASI was reduced from 12.7 to 0.7 (p=0.0001; mean EASI improvement = 88.8%); 94.3% (66/70), 92.9% (65/70), 90% (63/70), and 77.1% (54/70) of patients achieved absolute EASI scores < 7, 5, < 3, and < 1, respectively; mean BSA was reduced from 16.4% to 0.9% (p=0.0001; mean BSA improvement=92.5%); mean IGAxBSA was reduced from 53.5 to 1.6 (p=0.0001; mean IGAxBSA improvement=95.7%); and mean DLQI/CDLQI was reduced from 13 to 1.2 (p=0.0001; mean DLQI/CDLQI improvement=90.5%), with 84.6% (55/65) of patients achieving DLQI/CDLQI 0/1. UPA monotherapy was utilized in 38.9% (51/131) of cases. Common concomitant therapies included topical corticosteroids (56.5%, 74/131), systemic corticosteroids (5.3%, 7/131), and topical calcineurin inhibitors (3.8%, 5/131). Frequent AEs included: acne (18.3%, 24/131), hypertriglyceridemia (18.3%, 24/131), elevated creatine phosphokinase (12.2%, 16/131), herpes simplex (5.3%, 7/131), and transaminitis (5.3%, 7/131). Five patients (3.8%) discontinued UPA due to treatment-related AEs (myalgia/arthralgia [n=2]; gastrointestinal discomfort [n=1]; venous thromboembolism [n=1]; folliculitis [n=1]). No serious infections, tuberculosis, major adverse cardiovascular events, gastrointestinal perforation, or malignancy were observed in 67.4 patient-years of safety follow-up. Conclusions Our real-world study shows that UPA is an effective and safe therapy for AD, with high levels of skin clearance and a favorable safety profile between weeks 20-32. These results indicate that UPA may perform better in the real-world versus clinical trial setting, as compared to the Heads Up and Rising Up studies at week 24, specifically for IGA 0/1 and EASI75/EASI90/EASI100 achievement. This may be explained by less severe baseline disease severity in our study. Limitations of this study include its sample size and retrospective nature. [ABSTRACT FROM AUTHOR]

The article discusses a retrospective study on the real-world experience of using Spesolimab, an interleukin-36 receptor inhibitor, for treating generalized pustular psoriasis flares in adult patients. The study included five patients from Toronto, Canada, who showed significant improvement in their condition after treatment with Spesolimab, with no significant adverse events reported. The results of the study support the effectiveness and safety of Spesolimab for patients with active generalized pustular psoriasis flares, although the study's limitations include its retrospective nature, short follow-up period, and small sample size. [Extracted from the article]

Melanoma is the deadliest form of skin cancer in the world with a growing incidence in North America. Contemporary treatments for melanoma include surgical resection, chemotherapy, and radiotherapy. However, apart from resection in early melanoma, the prognosis of patients using these treatments is typically poor. In the past decade, there have been significant advancements in melanoma therapies. Immunotherapies such as ipilimumab and targeted therapies such as vemurafenib have emerged as a promising option for patients as seen in both scientific and clinical research. Furthermore, combination therapies are starting to be administered in the form of polychemotherapy, polyimmunotherapy, and biochemotherapy, of which some have shown promising outcomes in relative efficacy and safety due to their multiple targets. Alongside these treatments, new research has been conducted into the evidence-based use of natural health products (NHPs) and natural compounds (NCs) on melanoma which may provide a long-term and non-toxic form of complementary therapy. Nevertheless, there is a limited consolidation of the research conducted in emerging melanoma treatments which may be useful for researchers and clinicians. Thus, this review attempts to evaluate the therapeutic efficacy of current advancements in metastatic melanoma treatment by surveying new research into the molecular and cellular basis of treatments along with their clinical efficacy. In addition, this review aims to elucidate novel strategies that are currently being used and have the potential to be used in the future. [ABSTRACT FROM AUTHOR]

Most cancer therapeutics, such as tubulin-targeting chemotherapy drugs, cause cytotoxic, non-selective effects. These harmful side-effects drastically reduce the cancer patient's quality of life. Recently, researchers have focused their efforts on studying natural health products (NHP's) which have demonstrated the ability to selectively target cancer cells in cellular and animal models. However, the major hurdle of clinical validation remains. NHP's warrant further clinical investigation as a therapeutic option since they exhibit low toxicity, while retaining a selective effect. Additionally, they can sensitize cancerous cells to chemotherapy, which enhances the efficacy of chemotherapeutic drugs, indicating that they can be utilized as supplemental therapy. An additional area for further research is the investigation of drug–drug interactions between NHP's and chemotherapeutics. The objectives of this review are to report the most recent results from the field of anticancer NHP research, and to highlight the most recent advancements in possible supplemental therapeutic options. [ABSTRACT FROM AUTHOR]

Melanoma is the leading cause of skin-cancer related deaths in North America. Metastatic melanoma is difficult to treat and chemotherapies have limited success. Furthermore, chemotherapies lead to toxic side effects due to nonselective targeting of normal cells. Curcumin is a natural product of Curcuma longa (turmeric) and has been shown to possess anti-cancer activity. However, due to its poor bioavailability and stability, natural curcumin is not an effective cancer treatment. We tested synthetic analogs of curcumin that are more stable. One of these derivatives, Compound A, has shown significant anti-cancer efficacy in colon, leukemia, and triple-negative inflammatory breast cancer cells. However, the effects of Compound A against melanoma cells have not been studied before. In this study, for the first time, we demonstrated the efficacy of Compound A for the selective induction of apoptosis in melanoma cells and its interaction with tamoxifen, taxol, and cisplatin. We found that Compound A induced apoptosis selectively in human melanoma cells by increasing oxidative stress. The anti-cancer activity of Compound A was enhanced when combined with tamoxifen and the combination treatment did not result in significant toxicity to noncancerous cells. Additionally, Compound A did not interact negatively with the anti-cancer activity of taxol and cisplatin. These results indicate that Compound A could be developed as a selective and effective melanoma treatment either alone or in combination with other non-toxic agents like tamoxifen. [ABSTRACT FROM AUTHOR]