The latest medical research on Melanoma

The results of small studies suggest that off-label use of low-dose oral minoxidil (LDOM) may be safe and effective for patients with hair loss, but larger trials and standardized guidelines are lacking.

To create an expert consensus statement for LDOM prescribing for patients with hair loss.

The current literature on the pharmacological properties, adverse effect profile, and use of LDOM for patients with hair loss was reviewed. Topics of interest were identified, and a modified Delphi consensus process was created. A total of 43 hair loss specialist dermatologists from 12 countries participated in a modified Delphi process. Consensus was reached if at least 70% agreed or strongly agreed on a 5-point Likert scale.

Over 4 survey rounds, 180 items in the first round, 121 items in the second round, 16 items in the third round, and 11 items in the fourth round were considered and revised. A total of 76 items achieved consensus including diagnoses for which LDOM may provide direct or supportive benefit, indications for LDOM compared to topical minoxidil, dosing for adults (18 years and older) and adolescents (aged 12 to 17 years), contraindications, precautions, baseline evaluation, monitoring, adjunctive therapy, and specialty consultation. Pediatric use and dosing items for children younger than 12 years, and LDOM titration protocols fell short of consensus.

This international expert consensus statement regarding the off-label prescribing of LDOM for patients with hair loss can help guide clinical practice until more data emerge. Hair loss experts with experience treating pediatric patients were underrepresented on this expert panel. Future research should investigate best practices for LDOM use in pediatric patients. Other critical topics for further investigation include the comparative efficacy of topical minoxidil vs oral minoxidil, the safety of oral minoxidil for patients with a history of allergic contact dermatitis to topical minoxidil, the long-term safety of LDOM, and the use of other off-label forms of minoxidil, such as compounded formulations of oral minoxidil and sublingual minoxidil. As additional evidence-based data emerge, these recommendations should be updated.

The alpha-2 agonist xylazine is increasingly detected as an adulterant in illicitly manufactured fentanyl. There is concern that xylazine may be responsible for an emerging pattern of necrotizing wounds among people who use drugs, but the clinical features of wounds associated with xylazine remain poorly characterized.

To systematically characterize the location, wound bed surface, and chronicity of wounds among persons with confirmed xylazine exposure.

This case series at 3 academic medical hospitals in Philadelphia, Pennsylvania, included patients with emergency department or inpatient encounters from April 2022 to February 2023 who had a wound-related chief complaint and xylazine detected with urine gas chromatography-mass spectroscopy.

Xylazine.

The location, size, wound bed, and chronicity of wounds associated with xylazine using electronic medical record abstraction and Fisher exact tests.

Of 59 wounds from 29 unique patients with confirmed xylazine exposure (mean [SD] age, 39.4 [8.8] years; 15 [52%] male; all using fentanyl, and 23 [79%] routinely injecting opioids), 53 wounds (90%) were located on extremities, and 41 (69%) involved extensor surfaces. Five wounds (9%) involved exposed deep structures such as bone or tendon. Of 57 wounds with photographs, 34 (60%) had wound beds of predominantly devitalized tissue (eschar or slough). Based on patient report, 28 wounds (48%) were acute (<1 month old), 12 (20%) were subacute (present for 1-3 months), and 17 (29%) were chronic (developed ≥3 months prior). Subacute and chronic wounds were more often medium or large in size (odds ratio, 48.5; 95% CI, 8.2-1274.8; P < .001) and more frequently had devitalized wound beds (odds ratio, 9.5; 95% CI, 2.9-37.0; P < .001).

In this case series of hospitalized patients with confirmed xylazine exposure, wounds were commonly located on extensor surfaces of the extremities, frequently had devitalized tissue or exposed deep structures, and were more likely to have larger and necrotic wound beds the longer they had persisted. This systematic characterization of xylazine-associated wounds may inform identification, management, and research to address this emerging public health threat.

Defining meaningful improvement using the Total Vitiligo Area Scoring Index (T-VASI) and the Facial VASI (F-VASI) aids interpretation of findings from clinical trials evaluating vitiligo treatments; however, clear and clinically meaningful thresholds have not yet been established.

To assess concept validity and measurement performance of the T-VASI and F-VASI in patients with nonsegmental vitiligo and to identify meaningful change thresholds.

This mixed-methods study consisted of a secondary analysis of a phase 2 multicenter double-blind dose-ranging randomized clinical trial and embedded qualitative interviews conducted at 35 sites in Canada, France, Japan, and the US. The secondary analysis included the trial's adult patients with nonsegmental vitiligo (T-VASI ≥5 and F-VASI ≥0.5 at baseline). Psychometric performance of the T-VASI and F-VASI and thresholds for meaningful change were evaluated using clinician- and patient-reported information. The trial's embedded interviews were used to qualitatively assess content validity and patient perceptions of meaningful repigmentation. Data analyses were performed from March to July 2023.

Participants were randomized to 6-, 11-, or 22-mg/day upadacitinib or placebo for 24 weeks.

Psychometric performance of the T-VASI and F-VASI and thresholds for meaningful changed plus content validity and patient perceptions of meaningful repigmentation. Measurement instruments included the T-VASI, F-VASI, Vitiligo Noticeability Scale, Total-Patient Global Vitiligo Assessment, Face-Patient Global Vitiligo Assessment, Total-Physician Global Vitiligo Assessment (PhGVA-T), Face-Physician Global Vitiligo Assessment (PhGVA-F), Patient's Global Impression of Change-Vitiligo, Physician's Global Impression of Change-Vitiligo (PhGIC-V), Vitiligo Quality-of-Life Instrument, Dermatology Life Quality Index, the Hospital Anxiety and Depression Scale, and transcribed verbatim interviews with patients.

The psychometric analysis included 164 participants (mean [SD] age, 46 years; 103 [63%] females) and the qualitative analysis included 14 participants (mean [SD] age, 48.8 [12.2] years; 9 females [64%] and 5 males [36%]). Intraclass correlation coefficients were 0.98 for T-VASI and 0.99 for F-VASI in patients with clinically stable vitiligo between baseline and week 4, supporting test-retest reliability. At baseline and week 24, correlations were moderate to strong between T-VASI and PhGVA-T (r = 0.63-0.65) and between F-VASI and PhGVA-F (r = 0.65-0.71). Average baseline and week-24 VASI scores decreased with repigmentation (ie, increasing PhGVA scores). Least-square mean VASI scores increased with greater repigmentation as measured by the PhGIC-V. Least-square mean VASI scores also differed between patients with improved PhGIC-V and those with no change or worsened V-PhGIC scores. Using a multiple anchor approach, improvements of 30% in T-VASI and 50% in F-VASI scores reflected meaningful repigmentation between baseline and week 24.

This mixed-methods study found that the T-VASI and F-VASI are reliable, valid, able to differentiate between clinically distinct groups, and responsive in patients with nonsegmental vitiligo. The thresholds for meaningful change were lower than those historically used in clinical trials, suggesting that T-VASI 50 and F-VASI 75 are conservative estimates and reflect improvements that would be meaningful in patients with nonsegmental vitiligo.

ClinicalTrials.gov Identifier: NCT04927975.

There is poor accuracy and reproducibility for the histopathologic diagnosis of melanocytic skin lesions, and the provision of clinical information may improve this.

To examine the impact of clinical information on the histopathologic diagnosis of melanocytic skin lesions.

PubMed, Embase, and Cochrane Library were searched for new records published from January 2018 to January 2024. References included in the 2018 Cancer Council Australia evidence review were also screened, and forward and backward citation searches were conducted.

From 2224 records screened, 162 full-text studies were assessed, and 7 studies were included. Studies included pathologists from Austria, Germany, the US, Italy, the UK, and Australia. Patient populations had a mean age of 43 to 55 years and a proportion of female participants of 23% to 63%. The risk of bias assessment demonstrated that all studies had domains at unclear or high risk of bias. Clinical images increased diagnostic certainty (3 studies) and agreement between pathologists (2 studies) led to diagnostic upgrades in 7.6% to 16.7% of interpretations. Clinical diagnosis on the pathology requisition form reduced the odds of missing a melanoma with progression (1 study), while more clinical elements on the form correlated with higher re-excision rates (1 study). Among patients with distant metastases on long-term follow-up, a prior consensus diagnosis of melanoma was established on histopathology alone.

Providing clinical information to pathologists may improve diagnostic confidence and interobserver agreement and result in upgrading of the histopathologic diagnosis. While providing the clinical diagnosis may prevent missing a progressive melanoma, more research is needed to determine the appropriateness of histopathology upgrading when clinical images are provided and the impacts on patient outcomes.