Survival and Tumor Characteristics Of Patients Presenting With Single Primary Versus Second Primary Melanoma Lesions
Patients with second primary melanomas demonstrated a significant survival advantage and thinner lesions compared with those with single primary melanomas. The reported tumor distributions support the role of full body skin examinations, with attention to the region of initial diagnosis.
KEY FINDINGS: Patients with second primary melanomas demonstrated a significant survival advantage and thinner lesions compared with those with single primary melanomas. The reported tumor distributions support the role of full body skin examinations, with attention to the region of initial diagnosis.
BACKGROUND: Patients with single primary melanomas have an increased risk of developing subsequent melanomas. Secondary tumors diagnosed within and after 3 months are termed "synchronous" and "asynchronous," respectively. Purpose of the study is to compare tumor distributions and survival characteristics between patients with second primary melanomas and those with single primary melanomas.
DETAILS: Retrospective cohort study. Data were collected from an institutional database from 14,029 patients with a diagnosis of a primary melanoma seen between 1970 and 2004. The synchronous and asynchronous cohorts demonstrated significantly improved survival probabilities compared with the single primary cohort (P = .04 and .002, respectively). Single primary lesions (2.2 ± 2.3 mm) were significantly thicker than the first-identified synchronous (2.0 ± 1.7 mm) and asynchronous (1.7 ± 1.3 mm) lesions. Synchronous lesions were more likely to be anatomically concordant compared with asynchronous lesions (55.7% vs 38.2%, P < .001).
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Source: Sarver, M. M., Rames, J. D., Beasley, G. M., et al. (2023). Survival and Tumor Characteristics Of Patients Presenting With Single Primary Versus Second Primary Melanoma Lesions. Journal of the American Academy of Dermatology. 2023; 88(5): 1033-1039. Published: May, 2023. DOI: 10.1016/j.jaad.2022.04.046.
DMT310, A Novel Once-Weekly Topical Treatment For Patients With Moderate-To-Severe Acne Vulgaris
DMT310 once-weekly topical treatment significantly reduced both inflammatory and noninflammatory lesions and yielded a greater proportion of Investigator's Global Assessment treatment success at all time points in participants with moderate-to-severe acne.
Summary
Results Of A Phase 2B Randomized, Double-Blind, Placebo-Controlled Trial
[Posted 23/Oct/2023]
AUDIENCE: Dermatology, Pediatric, Family Medicine
KEY FINDINGS: DMT310 once-weekly topical treatment significantly reduced both inflammatory and noninflammatory lesions and yielded a greater proportion of Investigator's Global Assessment treatment success at all time points in participants with moderate-to-severe acne.
BACKGROUND: Poor patient adherence with antiacne medications is a common clinical challenge. DMT310, a natural, topical product with a once-weekly application schedule, may alleviate this obstacle. Purpose of this study is to evaluate the safety, tolerability, and efficacy of DMT310 in treating moderate-to-severe acne. This 12-week, randomized, double-blind, placebo-controlled, multicenter clinical trial enrolled participants 12 years and older with moderate-to-severe acne.
DETAILS: The intent-to-treat population included a total of 181 participants (DMT310, N = 91; placebo, N = 90). Participants who received DMT310 vs participants treated with placebo demonstrated a statistically significant greater reduction in the number of inflammatory and noninflammatory lesions at all time points: inflammatory lesion counts at week 12 (-15.64 vs -10.84, P < .001); noninflammatory lesion counts at week 12 (-18.26 vs -12.41, P < .001). DMT310-treated participants also had higher rates of Investigator's Global Assessment treatment success than participants in the placebo group at all time points: Investigator's Global Assessment at week 12 (44.40% vs 17.78%; P < .001). No serious treatment related adverse events occurred.
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Source: Eichenfield, L. F., DuBois, J. C., Gold, M. H., et al. (2023). DMT310, A Novel Once-Weekly Topical Treatment For Patients With Moderate-To-Severe Acne Vulgaris: Results Of A Phase 2B Randomized, Double-Blind, Placebo-Controlled Trial. JAAD. 2023; 89(5): 945-951. Published: November, 2023. DOI: 10.1016/j.jaad.2023.05.070.
Bath Psoralen Plus Ultraviolet-A Photochemotherapy for Chronic Graft-Versus-Host Disease
Bath PUVA is well-tolerated and effective for extensive cutaneous chronic graft-versus-host disease. It allows rapid tapering of adjuvant immunosuppressants; however, most patients require prolonged maintenance phototherapy.
KEY FINDINGS: Bath PUVA is well-tolerated and effective for extensive cutaneous chronic graft-versus-host disease. It allows rapid tapering of adjuvant immunosuppressants; however, most patients require prolonged maintenance phototherapy.
BACKGROUND: Chronic graft-versus-host disease is a severe complication of allogeneic stem cell and bone marrow transplantation. First-line immunosuppressive agents, such as steroids, are used to prevent this disease; however, they have multiple side effects. Therefore, bath psoralen plus ultraviolet-A (PUVA) is an alternative second-line treatment. This study aimed to evaluate the clinical efficacy of bath PUVA for managing chronic graft-versus-host disease.
DETAILS: This retrospective, case-control study included 14 patients with extensive cutaneous chronic graft-versus-host disease, resistant to systemic corticosteroid, treated with bath PUVA. Major and partial responses were defined as clinical improvements of >70% and 50-70%, respectively. We analyzed the graft-versus-host disease clinical presentation and timing after allogeneic stem cell and bone marrow transplantation, bath PUVA doses, background diseases, additional treatments, and adverse effects. Researchers observed eight major (three lichenoid and five sclerodermatoid) and six partial (three lichenoid and three sclerodermatoid) responses after a mean of 28 treatment sessions. After 6 to 25 months, four of the eight patients with sclerodermatoid lesions and all those with lichenoid lesions experienced relapse but responded to additional treatment cycles.
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Source: Kassem, R., Barzilai, A., Pras, E., et al. (2023). Bath Psoralen Plus Ultraviolet-A Photochemotherapy for Chronic Graft-Versus-Host Disease: A Retrospective Cohort Study. Int J Dermatol. 2023; 62(10): 1261-1265. Published: October, 2023. DOI: 10.1111/ijd.16806.
A Comprehensive Investigation of Novel and Traditional Inflammatory and Metabolic Markers as Predictive Indicators in Psoriasis
The absence of specificity of these markers for psoriasis limits their practical application. However, the development of new objective measures by using them in combination with specific data such as PASI will provide significant benefits in terms of disease diagnosis, follow-up, and treatment.
KEY FINDINGS: The absence of specificity of these markers for psoriasis limits their practical application. However, the development of new objective measures by using them in combination with specific data such as PASI will provide significant benefits in terms of disease diagnosis, follow-up, and treatment.
BACKGROUND: Psoriasis is a chronic inflammatory and papulosquamous dermatological disorder. While previous studies have discussed certain inflammatory markers for diagnosing and monitoring psoriasis, there is an absence of comprehensive research encompassing both novel and traditional inflammatory markers, as well as metabolic markers, in relation to psoriasis.
DETAILS: A total of 209 individuals participated, including 54 psoriasis patients and 155 controls. Psoriasis Area Severity Index (PASI) was calculated for the patient group. Potential predictive markers for psoriasis were identified: Uric acid/HDL ratio (UHR), D-dimer/albumin ratio (DAR), fibrinogen/albumin ratio (FAR), erythrocyte sedimentation rate, CRP, WBC, HOMA-IR, and vitamin D levels. Differences between groups and correlations with PASI and each other were analyzed using the Mann–Whitney U test and Spearman correlation coefficient. The results indicate that the patient group exhibited statistically significantly higher levels of UHR, FAR, CRP, WBC, and HOMA-IR. Upon analyzing the correlations between PASI and the identified markers, statistically significant positive correlation with WBC and negative correlation with vitamin D were observed. The correlations of PASI with other markers did not reach statistical significance. It should be underlined that our study was conducted in a predominantly mild-to-moderate patient population.
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Source: Metin, Z., Tur, K., Durmaz, K., et al. (2023). A Comprehensive Investigation of Novel and Traditional Inflammatory and Metabolic Markers as Predictive Indicators in Psoriasis. International Journal of Dermatology. 2023; 62(10): 1272-1280. Published: October, 2023. DOI: 10.1111/ijd.16813.
Adalimumab In Conjunction With Surgery Compared With Adalimumab Monotherapy For Hidradenitis Suppurativa
Combining adalimumab with surgery resulted in greater clinical effectiveness and improved quality of life after 12 months in patients with moderate to severe hidradenitis suppurativa.
Summary
A Randomized Controlled Trial In A Real-World Setting
[Posted 21/Sep/2023]
AUDIENCE: Dermatology, Family Medicine
KEY FINDINGS: Combining adalimumab with surgery resulted in greater clinical effectiveness and improved quality of life after 12 months in patients with moderate to severe hidradenitis suppurativa.
BACKGROUND: Adalimumab, the only biologic registered for hidradenitis suppurativa, shows clinical response in up to 60% of patients, leaving many patients in need for other treatment options such as surgery. Aim of the study is to compare the clinical effectiveness of adalimumab combined with surgery vs adalimumab monotherapy in patients with moderate to severe hidradenitis suppurativa.
DETAILS: A pragmatic Randomized Controlled Trial was performed from August 2018 to July 2022. Primary outcome was the difference in mean International Hidradenitis Suppurativa Severity Score System reduction after 12 months of treatment with the difference in mean Dermatology Life Quality Index reduction as a key secondary outcome. Thirty-one patients were included per arm. The mean International Hidradenitis Suppurativa Severity Score System at baseline was 23.9 ± 10.7 in the surgery group and 20.9 ± 16.4, in the monotherapy group. After 12 months of treatment the surgery group had a significantly greater reduction in International Hidradenitis Suppurativa Severity Score System compared with the monotherapy group (-19.1 ± 11.3 vs -7.8 ± 11.8, P < .001). Moreover, the surgery group showed a greater reduction in Dermatology Life Quality Index after treatment compared with the monotherapy group (-8.2 ± 6.2 vs -4 ± 7.7, P = .02). Limitations: The study follow-up was too short to assess surgical recurrence rates.
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Source: Aarts, P., van Huijstee, J. C., van der Zee, H. H., et al. (2023). Adalimumab In Conjunction With Surgery Compared With Adalimumab Monotherapy For Hidradenitis Suppurativa: A Randomized Controlled Trial In A Real-World Setting. Journal of the American Academy of Dermatology. 2023; 89(4): 677-684. Published: October, 2023. DOI: 10.1016/j.jaad.2023.04.034.
Lysosomal Function and Intracellular Position Determine the Malignant Phenotype in Malignant Melanoma
Rab7a overexpression is accompanied by reduced migration capacity. Taken together, the study emphasizes that alterations in lysosomal properties facilitate the malignant phenotype and declares the targeting of lysosomal function as a future therapeutic approach.
KEY FINDINGS: In addition, Rab7a overexpression is accompanied by reduced migration capacity. Taken together, the study emphasizes that alterations in lysosomal properties facilitate the malignant phenotype and declares the targeting of lysosomal function as a future therapeutic approach.
BACKGROUND: Lysosomes are central in cell homeostasis and participate in macromolecular degradation, plasma membrane repair, exosome release, cell adhesion/migration, and apoptosis. In cancer, alterations in lysosomal function and spatial distribution may facilitate disease progression.
DETAILS: In this study, authors show enhanced lysosomal activity in malignant melanoma cells compared with that in normal human melanocytes. Most lysosomes show perinuclear location in melanocytes, while they are more dispersed in melanoma, with retained proteolytic activity and low pH also in the peripheral population. Rab7a expression is lower in melanoma cells than in melanocytes, and by increasing Rab7a, lysosomes are relocated to the perinuclear region in melanoma. Exposure to the lysosome-destabilizing drug L-leucyl-L-leucine methyl ester causes higher damage in the perinuclear subset of lysosomes in melanomas, whereas differences in subpopulation susceptibility cannot be found in melanocytes. Interestingly, melanoma cells recruit the endosomal sorting complex required for transport-III core protein CHMP4B, involved in lysosomal membrane repair, rather than initiate lysophagy. However, when the perinuclear lysosomal position is promoted by Rab7a overexpression or kinesore treatment, lysophagy is increased.
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Copyright © The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. All rights reserved.
Source: Eriksson, I., Vainikka, L., Waster, P., et al. (2023). Lysosomal Function and Intracellular Position Determine the Malignant Phenotype in Malignant Melanoma. Journal of Investigative Dermatology. 2023; 143 (9): 1769-1778. Published: September, 2023. DOI: 10.1016/j.jid.2023.01.036.
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