Prognostic Role Of Microsatellites In Melanoma and Implications In The American Joint Committee On Cancer Classification System
Microsatellites were associated with other adverse melanoma prognostic factors. A multivariate Cox regression analysis showed that they are an independent risk factor for worse OS, MSS, and disease-free survival.
KEY FINDINGS: Microsatellites were associated with other adverse melanoma prognostic factors. A multivariate Cox regression analysis showed that they are an independent risk factor for worse OS, MSS, and disease-free survival. Patients with stage IIIB melanoma with microsatellites had worse OS and MSS, whereas patients with stage IIIC melanoma had worse OS but not MSS.
BACKGROUND: There is limited information on microsatellite survival outcomes in patients with melanoma. Purpose of this study is to evaluate survival outcomes in patients with microsatellites, assess their role within stage III stratification of the American Joint Committee on Cancer classification, and assess the results of sentinel lymph node biopsies in patients with microsatellites.
DETAILS: A retrospective bicenter cohort study from 1998 to 2019 included patients with a diagnosis of invasive cutaneous melanoma. Of a total of 5216 patients, 108 (2.1%) had microsatellites at initial staging. Survival analysis showed that microsatellites were an independent risk factor with decreased overall survival (OS), melanoma-specific survival (MSS), and disease-free survival, with hazard ratios of 1.57, 1.76, and 1.76, respectively. Stratified analysis in patients with stage III melanoma showed a 5-year OS of 35% (95% CI, 17.3%-73.4%) and a MSS of 45% (95% CI, 23.1-87.5) for patients with stage IIIB melanoma with microsatellites.
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Source: Riquelme-Mc Loughlin, C., Sandoval-Clavijo, A., Blnco de Tord, M., et al. (2023). Prognostic Role Of Microsatellites In Melanoma and Implications In The American Joint Committee On Cancer Classification System: A Cohort Study. Journal of the American Academy of Dermatology. 2023; 88(2): 338-347. Published: February, 2023. DOI: 10.1016/j.jaad.2022.10.027.
Increasing Threat of Spread of Antimicrobial-resistant Fungus in Healthcare Facilities
C. auris case counts may also have increased because of enhanced efforts to detect cases, including increased colonization screening, a test to see if someone has the fungus somewhere on their body but does not have an infection or symptoms of infection.
KEY FINDINGS: C. auris case counts have increased for many reasons, including poor general infection prevention and control (IPC) practices in healthcare facilities. Case counts may also have increased because of enhanced efforts to detect cases, including increased colonization screening, a test to see if someone has the fungus somewhere on their body but does not have an infection or symptoms of infection. The timing of this increase and findings from public health investigations suggest C. auris spread may have worsened due to strain on healthcare and public health systems during the COVID-19 pandemic.
BACKGROUND: Candida auris (C. auris), an emerging fungus considered an urgent antimicrobial resistance (AR) threat, spread at an alarming rate in U.S. healthcare facilities in 2020-2021, according to data from the Centers for Disease Control and Prevention (CDC) published in the Annals of Internal Medicine. Equally concerning was a tripling in 2021 of the number of cases that were resistant to echinocandins, the antifungal medicine most recommended for treatment of C. auris infections. In general, C. auris is not a threat to healthy people. People who are very sick, have invasive medical devices, or have long or frequent stays in healthcare facilities are at increased risk for acquiring C. auris. CDC has deemed C. auris as an urgent AR threat, because it is often resistant to multiple antifungal drugs, spreads easily in healthcare facilities, and can cause severe infections with high death rates.
DETAILS: "The rapid rise and geographic spread of cases is concerning and emphasizes the need for continued surveillance, expanded lab capacity, quicker diagnostic tests, and adherence to proven infection prevention and control," said CDC epidemiologist Dr. Meghan Lyman, lead author of the paper.
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As further explained in the article, C. auris has spread in the United States since it was first reported in 2016, with a total of 3,270 clinical cases (in which infection is present) and 7,413 screening cases (in which the fungus is detected but not causing infection) reported through December 31, 2021. Clinical cases have increased each year since 2016, with the most rapid rise occurring during 2020-2021. CDC has continued to see an increase in case counts for 2022. During 2019-2021, 17 states identified their first C. auris case ever. Nationwide, clinical cases rose from 476 in 2019 to 1,471 in 2021. Screening cases tripled from 2020 to 2021, for a total of 4,041. Screening is important to prevent spread by identifying patients carrying the fungus so that infection prevention controls can be used.
The CDC's Antimicrobial Resistance Laboratory Network, which provides nationwide lab capacity to rapidly detect antimicrobial resistance and inform local responses to prevent spread and protect people, provided some of the data for this report. CDC worked to significantly strengthen laboratory capacity, including in state, territorial, and local health departments, through supplemental funding supported by the American Rescue Plan Act. These efforts include increasing susceptibility testing capacity for C. auris from seven Regional Labs to more than 26 labs nationwide.
CDC continues to work with state, local, and territorial health departments and other partners to address this emerging threat to public health. Review more information on C. auris, the Antimicrobial Resistance Threats Report that identified C. auris as an urgent threat in the United States, or the WHO fungal priority pathogen list that identifies C. auris as a priority globally.
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Source: Increasing Threat of Spread of Antimicrobial-resistant Fungus in Healthcare Facilities. Centers for Disease Control and Prevention. 2023; 320. Published: March 20, 2023. https://www.cdc.gov/media/releases/2023/p0320-cauris.html.
Evaluation and Characterization of Facial Skin Aging Using Optical Coherence Tomography
The results illustrate a decline in skin density with chronological age. It was illustrated that structural change in the epidermis and dermis does occur,
KEY FINDINGS: OCT is an effective method for evaluating changes in aging skin. The results illustrate a decline in skin density with chronological age. Additionally, it was illustrated that structural change in the epidermis and dermis does occur, however on a microscopic scale, there are no significant differences based on laterality. OCT holds promise as a noninvasive technique for characterization of aging skin. Its utility and application in the clinical management and treatment of aged skin requires further research; however, the technology has potential to personalize therapies based on objective findings.
BACKGROUND: The skin aging exposome encompasses internal and external factors that contribute to clinical signs of facial aging. Aging skin can be characterized by distinctive features such as wrinkles, lentigines, elastosis, and roughness. Optical coherence tomography (OCT) is capable of noninvasively measuring skin characteristics. This study aimed to assess bilateral features using OCT to explore temporal skin changes among decades and potential changes in facial skin aging based on laterality.
DETAILS: A total of 97 subjects between 20 and 89 years old with Fitzpatrick skin types I to IV were enrolled. VivoSight, a Multi-Beam OCT system intended to gather topographical and histological images of skin, was used to scan the area inferolateral to the lateral canthus, bilaterally. Investigators compared characteristics of skin roughness, attenuation coefficient and blood flow across age groups and based on laterality to determine any differences. Only data from successful OCT scans were used. Seventy subjects, 10 from each specified decade, had successful bilateral scans and were thus included in the analysis. Chronological aging was characterized by significantly decreased dermal attenuation coefficient with increased age. Skin roughness measurements showed trends of increased roughness with age; however, no statistically significant changes were seen between groups. Qualitative differences amongst scans taken on right and left sides of the face showed no significance regarding roughness, density or blood flow at depths ranging from 0.05 to 0.5 mm.
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Source: Vingan, N. R., Parsa, S., Barillas, J., et al. (2023). Evaluation and Characterization of Facial Skin Aging Using Optical Coherence Tomography. Lasers Surg. Med.. 2023; 55(1): 23-24. Published: January, 2023. DOI: 10.1002/lsm.23611.
Sentinel Lymph Node Biopsy In Patients with T1A Cutaneous Malignant Melanoma
SLN+ is low in patients with T1a melanomas, but younger age, lymphovascular invasion, mitogenicity, and head/neck primary site appear to confer a higher risk of SLN+.
KEY FINDINGS: SLN+ is low in patients with T1a melanomas, but younger age, lymphovascular invasion, mitogenicity, and head/neck primary site appear to confer a higher risk of SLN+.
BACKGROUND: Sentinel lymph node biopsy is not routinely recommended for T1a cutaneous melanoma due to the overall low risk of positivity. Prognostic factors for positive sentinel lymph node (SLN+) in this population are poorly characterized. Aim of this study was to determine factors associated with SLN+ in patients with T1a melanoma
DETAILS: Patients with pathologic T1a (<0.80 mm, nonulcerated) cutaneous melanoma from 5 high-volume melanoma centers from 2001 to 2020 who underwent wide local excision with sentinel lymph node biopsy were included in the study. Patient and tumor characteristics associated with SLN+ were analyzed by univariate and multivariable logistic regression analyses. Age was dichotomized into <=42 (25% quartile cutoff) and >42 years. Of the 965 patients identified, the overall SLN+ was 4.4% (N = 43). Factors associated with SLN+ were age <=42 years (7.5% vs 3.7%; odds ratio [OR], 2.14; P = .03), head/neck primary tumor location (9.2% vs 4%; OR, 2.75; P = .04), lymphovascular invasion (21.4% vs 4.2%; OR, 5.64; P = .01), and >=2 mitoses/mm2 (8.2% vs 3.4%; OR, 2.31; P = .03). Patients <42 years with >=2 mitoses/mm2 (N = 38) had a SLN+ rate of 18.4%.
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Source: Shannon, A. B., Sharon, C. E., Straker III, R. J., et al. (2023). Sentinel Lymph Node Biopsy In Patients With T1A Cutaneous Malignant Melanoma: A Multicenter Cohort Study. JAAD. 2023; 88(1): 52-59. Published: January, 2023. DOI: 10.1016/j.jaad.2022.09.040.
Study of Purine Derivatives and Their Relation To Renal Disorders In Patients With Psoriasis
The findings suggest that apremilast was a safe and efficacious add-on treatment in recalcitrant dermatomyositis, with an overall response rate of 87.5% and associations with downregulation of multiple inflammatory pathways.
KEY FINDINGS: Pso, being a hyperproliferative disease, is associated with hyperuricemia, which has a harmful effect on kidney function. The related PDs may be unique serological biomarkers for patients with Pso who are at high risk of developing renal abnormalities, especially with higher severity scores.
BACKGROUND: Psoriasis (Pso) is a chronic proliferative skin condition associated with hyperuricemia that may impair renal function.
DETAILS: This case–control study comprises 30 psoriatic patients and 30 age- and sex-matched healthy controls. The enzyme-linked immunosorbent assay (ELISA) was used to assess serum xanthine oxidase (XO) and urine albumin levels. Serum uric acid (SUA) and urinary creatinine were measured using the colorimetric method. There was a rise in the related PDs levels in patients with Pso compared to controls, as evidenced by the enhanced SUA levels (p 0.001) and XO levels (p 0.001). The presence of the related PDs in the serum was linked to the severity of Pso, and there was also a connection between the related PDs levels in the blood and indicators of renal dysfunction. Moreover, SUA and urinary albumin creatinine ratio (UACR) were found to be significantly correlated (r = 0.371 and p = 0.044), as were XO and UACR (r = 0.422 and p = 0.020). In psoriatic patients with itching and palmoplantar affection, mean SUA levels were considerably more significant than those in other instances ( < p = 0.005 and p = 0.018, respectively).
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Source: Bazid, H. A. S., Shoeib, M. A., El-Saued, S., et al. (2022). Study of Purine Derivatives And Their Relation To Renal Disorders In Patients With Psoriasis. International Journal of Dermatology. 2023; 62(1): 73-78. Published: January, 2023. DOI: 10.1111/ijd.16343.
Apremilast in Recalcitrant Cutaneous Dermatomyositis
The findings suggest that apremilast was a safe and efficacious add-on treatment in recalcitrant dermatomyositis, with an overall response rate of 87.5% and associations with downregulation of multiple inflammatory pathways.
KEY FINDINGS: These findings suggest that apremilast was a safe and efficacious add-on treatment in recalcitrant dermatomyositis, with an overall response rate of 87.5% and associations with downregulation of multiple inflammatory pathways.
BACKGROUND: Cutaneous disease in dermatomyositis has no standardized treatment approach and so presents a challenging task for patients and clinicians. Purpose of this trial was to study the efficacy and safety of apremilast as an add-on therapy in patients with recalcitrant cutaneous dermatomyositis.
DETAILS: This phase 2a, open-label, single-arm nonrandomized controlled trial was conducted at a single center from June 2018 to June 2021. Participants were 8 patients with recalcitrant cutaneous dermatomyositis, defined by a cutaneous disease activity severity index (CDASI) score greater than 5 despite treatment with steroids, steroid-sparing agents, or both. Data were analyzed from June 2018 to June 2021. The primary outcome was the overall response rate (ORR) at 3 months. Key secondary outcomes were the safety and toxicity of apremilast and the durability of response at 6 months. The CDASI, muscle score, dermatology life quality index (DLQI), and depression assessments were performed at baseline and regularly until month 7. Skin biopsies were performed at baseline and 3 months after apremilast (defined as 3 months into active apremilast therapy) and tested for gene expression profiling and immunohistochemical stains. Adverse events were assessed using the Common Terminology Criteria for Adverse Events version 5.0. Among 8 patients with recalcitrant cutaneous dermatomyositis (all women; mean [SD] age, 54 [15.9] years), a response was found at 3 months after apremilast among 7 patients (ORR, 87.5%). The mean (SD) decrease in CDASI was 12.9 (6.3) points at 3 months (P .001). Apremilast was well tolerated, with no grade 3 or higher adverse events. Sequencing of RNA was performed on skin biopsies taken from 7 patients at baseline and at 3 months after therapy. Appropriate negative (ie, no primary antibody) and positive (ie, tonsil and spleen) controls were stained in parallel with each set of slides studied. Of 39,076 expressed genes, there were 195 whose expression changed 2-fold or more at P < .01 (123 downregulated and 72 upregulated genes). Gene set enrichment analysis identified 13 pathways in which apremilast was associated with downregulated expression, notably signal transducers and activators of transcription 1 (STAT1), STAT3, interleukin 4 (IL-4), IL-6, IL-12, IL-23, interferon γ (IFNy), and tumor necrosis factor α (TNFα) pathways. In immunohistochemical staining, there was a mean (SD) decrease in phosphorylation levels STAT1 (22.3% [28.3%] positive cells) and STAT3 (13.4% [11.6%] positive cells) at the protein level, a downstream signaling pathway for the downregulated cytokines.
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Source: Bitar, C., Ninh, T., Brag, K., et al. (2022). Apremilast in Recalcitrant Cutaneous Dermatomyositis: A Nonrandomized Controlled Trial. JAMA Dermatol. 2022;158(12): 1357-1366. Published: December, 2022. DOI: 0.1001/jamadermatol.2022.3917.
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