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Journal of Plastic, Reconstructive &... Feb 2023Treatment indications of congenital melanocytic naevi (CMN) have shifted from the prevention of malignant transformation more towards the improvement of appearance and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Treatment indications of congenital melanocytic naevi (CMN) have shifted from the prevention of malignant transformation more towards the improvement of appearance and psychosocial health. Surgical excision is often preferred, but its safety and effectiveness remain unclear.
OBJECTIVE
To assess the outcomes of surgical excision of medium-to-giant CMN.
PRIMARY OUTCOME
safety (complications).
SECONDARY OUTCOME
effectiveness (satisfaction and CMN core outcomes).
METHODS
PubMed, EMBASE, and CENTRAL were searched for studies on the excision of medium-to-giant CMN and/or CMN requiring reconstruction or serial excision. Meta-analyses of safety per patient were conducted, and pooled outcomes of safety and effectiveness were presented in summary-of-findings tables.
RESULTS
A total of 1444 studies were found, of which 22 were included, evaluating 643 eligible patients. Study quality varied, and reporting of baseline characteristics and outcomes was heterogeneous. Pooled proportions were overall 9.8% for major wound-related complications, 1.2% for minor wound-related complications, 1.2% for scar-related complications, and 4.3% for anatomical deformities. For large/giant CMN, complication rates were, respectively, 23.1%, 2.9%, 12.9%, and 2.4%; and for CMN with eyelid involvement, 0.5%, 3.3%, 0.4%, and 54.2%. Patients rated their satisfaction with the cosmetic outcome as 24.4% excellent, 71.0% good, and 4.6% poor/moderate. Physicians rated this as 18.3% excellent, 70.1% good, and 11.7% poor/moderate. Thirty-five other outcomes of effectiveness were summarized. However, many were rarely reported.
CONCLUSIONS
Surgical excision of CMN appears to be safe and effective in many cases, depending on CMN size and location. Major wound-related complications and scar-related complications occurred more frequently with large/giant CMN, whereas anatomical deformities occurred with the majority of CMN with eyelid involvement.
Topics: Humans; Cicatrix; Skin Neoplasms; Nevus, Pigmented; Cell Transformation, Neoplastic
PubMed: 36652871
DOI: 10.1016/j.bjps.2022.10.048 -
The Cochrane Database of Systematic... Aug 2019Chronic venous insufficiency (CVI) is a progressive and common disease that affects the superficial and deep venous systems of the lower limbs. CVI is characterised by...
BACKGROUND
Chronic venous insufficiency (CVI) is a progressive and common disease that affects the superficial and deep venous systems of the lower limbs. CVI is characterised by valvular incompetence, reflux, venous obstruction, or a combination of these with consequent distal venous hypertension. Clinical manifestations of CVI include oedema, pain, skin changes, ulcerations and dilated skin veins in the lower limbs. It can result in a large financial burden on health systems. There is a wide variety of treatment options or therapies for CVI, ranging from surgery and medication to compression and physiotherapy. Balneotherapy (treatments involving water) is a relatively cheap option and potentially efficient way to deliver physical therapy for people with CVI.
OBJECTIVES
To assess the efficacy and safety of balneotherapy for the treatment of people with chronic venous insufficiency (CVI).
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and the Clinical Trials.gov trials register to August 2018. We searched the LILACS and IBECS databases. We also checked references, searched citations and contacted study authors to identify additional studies.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials comparing balneotherapy with no treatment or other types of treatment for CVI. We also included studies that used a combination of treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed studies retrieved by the search strategies. Both review authors independently assessed selected studies for complete analysis. We resolved conflicts through discussion. We attempted to contact trial authors for missing data, obtaining additional information. For binary outcomes (leg ulcer incidence and adverse events), we presented the results using odds ratio (OR) with 95% confidence intervals (CI). For continuous outcomes (disease severity, health-related quality of life (HRQoL), pain, oedema, skin pigmentation), we presented the results as a mean difference (MD) with 95% CI.
MAIN RESULTS
We included seven randomised controlled trials with 891 participants (outpatients in secondary care). We found no quasi-randomised controlled trials. Six studies (836 participants) evaluated balneotherapy versus no treatment. One study evaluated balneotherapy versus a phlebotonic drug (melilotus officinalis) (55 participants). There was a lack of blinding of participants and investigators, imprecision and inconsistency, which downgraded the certainty of the evidence.For the balneotherapy versus no treatment comparison, there probably was no improvement in favour of balneotherapy in disease severity signs and symptom score as assessed using the Venous Clinical Severity Score (VCSS) (MD -1.66, 95% CI -4.14 to 0.83; 2 studies, 484 participants; moderate-certainty evidence). Balneotherapy probably resulted in a moderate improvement in HRQoL as assessed by the Chronic Venous Insufficiency Questionnaire 2 (CVIQ2) at three months (MD -9.38, 95% CI -18.18 to -0.57; 2 studies, 149 participants; moderate-certainty evidence), nine months (MD -10.46, 95% CI -11.81 to -9.11; 1 study; 55 participants; moderate-certainty evidence), and 12 months (MD -4.99, 95% CI -9.19 to -0.78; 2 studies, 455 participants; moderate-certainty evidence). There was no clear difference in HRQoL between balneotherapy and no treatment at six months (MD -1.64, 95% CI -9.18 to 5.89; 2 studies, 445 participants; moderate-certainty evidence). Balneotherapy probably slightly improved pain compared with no treatment (MD -1.23, 95% CI -1.33 to -1.13; 1 study; 390 participants; moderate-certainty evidence). There was no clear effect related to oedema between the two groups at 24 days (MD 43.28 mL, 95% CI -102.74 to 189.30; 2 studies, 153 participants; very-low certainty evidence). There probably was no improvement in favour of balneotherapy in the incidence of leg ulcers (OR 1.69, 95% CI 0.82 to 3.48; 2 studies, 449 participants; moderate-certainty evidence). There was probably a reduction in incidence of skin pigmentation changes in favour of balneotherapy at 12 months (pigmentation index: MD -3.59, 95% CI -4.02 to -3.16; 1 study; 59 participants; low-certainty evidence). The main complications reported included erysipelas (OR 2.58, 95% CI 0.65 to 10.22; 2 studies, 519 participants; moderate-certainty evidence), thromboembolic events (OR 0.35, 95% CI 0.09 to 1.42; 3 studies, 584 participants; moderate-certainty evidence) and palpitations (OR 0.33, 95% CI 0.01 to 8.52; 1 study; 59 participants; low-certainty evidence), with no clear evidence of an increase in reported adverse effects with balneotherapy. There were no serious adverse events reported in any of the studies.For the balneotherapy versus a phlebotonic drug (melilotus officinalis) comparison, we observed no clear difference in pain symptoms (OR 0.29, 95% CI 0.03 to 2.87; 1 study; 35 participants; very low-certainty evidence) and oedema (OR 0.21, 95% CI 0.02 to 2.27; 1 study; 35 participants; very low-certainty evidence). This single study did not report on the other outcomes of interest.
AUTHORS' CONCLUSIONS
We identified moderate- to low-certainty evidence that suggests that balneotherapy may result in a moderate improvement in pain, quality of life and skin pigmentation changes and has no clear effect on disease severity signs and symptoms score, adverse effects, leg ulcers and oedema when compared with no treatment. For future studies, measurements of outcomes such as disease severity sign and symptom score, quality of life, pain and oedema and choice of time points during follow-up must be standardised for adequate comparison between trials.
Topics: Balneology; Edema; Humans; Leg Ulcer; Pain Management; Quality of Life; Randomized Controlled Trials as Topic; Venous Insufficiency
PubMed: 31449319
DOI: 10.1002/14651858.CD013085.pub2 -
Journal of Clinical Medicine May 2020Since the efficacy of ranibizumab (RBZ), bevacizumab (BVZ) and aflibercept (AFB) is comparable in neovascular age-related macular degeneration (AMD), we conducted a... (Review)
Review
Comparative Safety of Bevacizumab, Ranibizumab, and Aflibercept for Treatment of Neovascular Age-Related Macular Degeneration (AMD): A Systematic Review and Network Meta-Analysis of Direct Comparative Studies.
BACKGROUND
Since the efficacy of ranibizumab (RBZ), bevacizumab (BVZ) and aflibercept (AFB) is comparable in neovascular age-related macular degeneration (AMD), we conducted a systematic review and meta-analysis to evaluate the long-term safety profiles of these agents, including ocular safety.
METHODS
Systematic review identifying randomized controlled trials (RCTs) comparing RBZ, BVZ and AFB directly published before March 2019. Serious ocular adverse events (SOAE) of special interest were endophthalmitis, pseudo-endophthalmitis, retinal pigment epithelium tear and newly identified macular atrophy.
RESULTS
Thirteen RCTs selected for meta-analysis (4952 patients, 8723 people-years follow-up): 10 compared RBZ vs. BVZ and three RBZ vs. AFB. There were no significant differences in almost all adverse events (systemic and ocular) between BVZ, RBZ and AFB in up to two years' follow-up. Macular atrophy was reported heterogeneously and not reported as SOAE in most trials.
CONCLUSIONS
Direct comparison of RBZ, BVZ and AFB safety profiles in the RCT network meta-analytical setting have not revealed a consistent benefit of these three commonly used anti-vascular endothelial growth factor (anti-VEGF) agents in AMD. Network model ranking highlighted potential benefits of RBZ in terms of a systemic safety profile; however, this appears a hypothesis rather than a conclusion. Newly identified macular atrophy is underestimated in RCTs-future real-world data should be focused on SOAE.
PubMed: 32443612
DOI: 10.3390/jcm9051522 -
Orphanet Journal of Rare Diseases Jul 2019Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis,... (Review)
Review
Hereditary hemochromatosis (HH) is a genetic disorder that causes excess absorption of iron and can lead to a variety of complications including liver cirrhosis, arthritis, abnormal skin pigmentation, cardiomyopathy, hypogonadism, and diabetes. Hemojuvelin (HJV) is the causative gene of a rare subtype of HH worldwide. This study aims to systematically review the genotypic and phenotypic spectra of HJV-HH in multiple ethnicities, and to explore the genotype-phenotype correlations. A comprehensive search of PubMed database was conducted. Data were extracted from 57 peer-reviewed original articles including 132 cases with HJV-HH of multiple ethnicities, involving 117 biallelic cases and 15 heterozygotes. Among the biallelic cases, male and female probands of Caucasian ancestry were equally affected, whereas males were more often affected among East Asians (P=1.72×10). Hepatic iron deposition and hypogonadism were the most frequently reported complications. Hypogonadism and arthropathy were more prevalent in Caucasians than in East Asians (P=9.30×10, 1.69×10). Among the recurrent mutations, G320V (45 unrelated cases) and L101P (7 unrelated cases) were detected most frequently and restricted to Caucasians. [Q6H; C321*] was predominant in Chinese patients (6 unrelated cases). I281T (Chinese and Greek), A310G (Brazilian and African American), and R385* (Italian and North African) were reported across different ethnicities. In genotype-phenotype correlation analyses, 91.30% of homozygotes with exon 2-3 mutations developed early-onset HH compared to 66.00% of those with exon 4 mutations (P=2.40×10). Hypogonadism occurred more frequently in homozygotes with missense mutations (72.55%) than in those with nonsense mutations (35.71%; P=2.43×10). Liver biopsy was accepted by more probands with frame-shift or missense mutations (85.71% and 60.78%, respectively) than by those with nonsense mutations (28.57%; P=2.37×10, 3.93×10). The present review suggests that patients' ethnicity, geographical region, and genetic predisposition should be considered in the diagnosis, prognosis and management of HJV-HH.
Topics: Female; Humans; Male; alpha-Galactosidase; Cross-Sectional Studies; Genotype; Hemochromatosis; Mutation; Hemochromatosis Protein
PubMed: 31286966
DOI: 10.1186/s13023-019-1097-2 -
Heart Failure Reviews Sep 2022Left atrial (LA) structure and function in heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF) is only established in small studies. Therefore,... (Meta-Analysis)
Meta-Analysis Review
Left atrial (LA) structure and function in heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF) is only established in small studies. Therefore, we conducted a systematic review of LA structure and function in order to find differences between patients with HFrEF and HFpEF. English literature on LA structure and function using echocardiography was reviewed to calculate pooled prevalence and weighted mean differences (WMD). A total of 61 studies, comprising 8806 patients with HFrEF and 9928 patients with HFpEF, were included. The pooled prevalence of atrial fibrillation (AF) was 34.4% versus 42.8% in the acute inpatient setting, and 20.1% versus 33.1% in the chronic outpatient setting when comparing between HFrEF and HFpEF. LA volume index (LAVi), LA reservoir global longitudinal strain (LAGLS), and E/e' was 59.7 versus 52.7 ml/m, 9.0% versus 18.9%, and 18.5 versus 14.0 in the acute inpatient setting, and 48.3 versus 38.2 ml/m, 12.8% versus 23.4%, and 16.9 versus 13.5 in the chronic outpatient setting when comparing HFrEF versus HFpEF, respectively. The relationship between LAVi and LAGLS was significant in HFpEF, but not in HFrEF. Also, in those studies that directly compared patients with HFrEF versus HFpEF, those with HFrEF had worse LAGLS [WMD = 16.3% (22.05,8.61); p < 0.001], and higher E/e' [WMD = -0.40 (-0.56, -0.24); p < 0.05], while LAVi was comparable. When focusing on acute hospitalized patients, E/e' was comparable between patients with HFrEF and HFpEF. Despite the higher burden of AF in HFpEF, patients with HFrEF had worse LA global function. Left atrial myopathy is not specifically related to HFpEF.
Topics: Atrial Fibrillation; Echocardiography; Heart Failure; Humans; Prognosis; Stroke Volume; Ventricular Function, Left
PubMed: 35079942
DOI: 10.1007/s10741-021-10204-8 -
3 Biotech Oct 2023Drought stress remains one of the most detrimental environmental constraints that hampers plant growth and development resulting in reduced yield and leading to economic... (Review)
Review
Drought stress remains one of the most detrimental environmental constraints that hampers plant growth and development resulting in reduced yield and leading to economic losses. Studies have highlighted the beneficial role of carbon-based nanomaterials (NMs) such as multiwalled carbon nanotubes (MWNTs), single-walled carbon nanotubes (SWNTs), graphene, fullerene, and metal-based nanoparticles (NPs) (Ag, Au, Cu, FeO, TiO, and ZnO) in plants under unfavorable conditions such as drought. NPs help plants cope with drought by improving plant growth indices and enhancing biomass. It improves water and nutrient uptake and utilization. It helps retain water by altering the cell walls and regulating stomatal closure. The photosynthetic parameters in NP-treated plants reportedly improved with the increase in pigment content and rate of photosynthesis. Due to NP exposure, the activation of enzymatic and nonenzymatic antioxidants has reportedly improved. These antioxidants play a significant role in the defense system against stress. Studies have reported the accumulation of osmolytes and secondary metabolites. Osmolytes scavenge reactive oxygen species, which can cause oxidative stress in plants. Secondary metabolites are involved in the water retention process, thus improving plant coping strategies with stress. The deleterious effects of drought stress are alleviated by reducing malondialdehyde resulting from lipid peroxidation. Reactive oxygen species accumulation is also controlled with NP treatment. Furthermore, NPs have been reported to regulate the expression of drought-responsive genes and the biosynthesis of phytohormones such as abscisic acid, auxin, gibberellin, and cytokinin, which help plants defend against drought stress. This study reviewed 72 journal articles from 192 Google Scholar, ScienceDirect, and PubMed papers. In this review, we have discussed the impact of NP treatment on morphological, physio-biochemical, and molecular responses in monocot and dicot plants under drought conditions with an emphasis on NP uptake, transportation, and localization.
PubMed: 37693636
DOI: 10.1007/s13205-023-03751-4 -
Diabetes, Metabolic Syndrome and... 2020Carotenoids are a large group of natural pigments that occur in many foods, fruits, and vegetables. Several studies have shown a number of biological properties of... (Review)
Review
BACKGROUND
Carotenoids are a large group of natural pigments that occur in many foods, fruits, and vegetables. Several studies have shown a number of biological properties of carotenoids, particularly beneficial impacts on cancer, metabolic, neurodegenerative, and cardiovascular diseases. However, recent evidence has shown that these compounds could prevent, delay, and ameliorate diabetic retinopathy (DR). The aim of current study was to review the therapeutic effects of carotenoids in the treatment of DR and discuss the molecular mechanisms that are behind these pharmacological activities.
METHODS
Six online databases (Medline/PubMed, Scopus, Web of Knowledge, Embase, ScienceDirect, and ProQuest) were searched until September 2019. The systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist.
RESULTS
A total of 25 studies were included after the final retrieval. A relationship was observed between carotenoids and management of DR. Findings also demonstrated that the underlying mechanism of beneficial effects of these compounds was antioxidant, anti-inflammatory, anti-angiogenic, and neuroprotective properties.
CONCLUSION
Carotenoids potentially delay the initiation and prevent the progression of DR; however, ample preclinical studies are required to confirm their effect, and adequate clinical trials are needed to really understand how well these compounds influence DR among humans.
PubMed: 32753919
DOI: 10.2147/DMSO.S255783 -
Critical Reviews in Food Science and... 2023Anthocyanins (ACN), the sub-class of (poly)phenols responsible for the red-blue-purple pigmentation of fruit and vegetables, have gained considerable interest in sport... (Meta-Analysis)
Meta-Analysis
Anthocyanins (ACN), the sub-class of (poly)phenols responsible for the red-blue-purple pigmentation of fruit and vegetables, have gained considerable interest in sport and exercise research due to their potential to facilitate exercise recovery. A systematic literature search was performed using PubMed, The Cochrane Library, MEDLINE, SPORTDiscus and CINAHL. Thirty nine studies were included and the standardized mean difference (Hedges ) for creatine kinase (CK), anti-oxidative and inflammatory markers, strength, power and delayed onset muscle soreness (DOMS) indices were pooled in separate meta-analyses; meta-regression was also performed on reported ACN dose. Immediately post-exercise there was an increase in antioxidant capacity (: 0.56) and reduced C reactive protein (: -0.24) and tumor necrosis factor α (: -40); ≤ 0.02. Strength was improved with ACN at all time points (: 0.45-0.67). DOMS (: -0.23) was lower 24 hours post-exercise and power was improved 24 hours (: 0.62) and 48 hours (: 0.57) post exercise. The CK was lower 48 hours post-exercise (: -0.31) and there was a trend for a positive association with ACN dose ( = 0.057). This systematic review provides new data showing ACN-rich foods promote functional and subjective recovery likely due to the antioxidant and anti-inflammatory properties of ACN.
Topics: Humans; Antioxidants; Anthocyanins; Exercise; Myalgia; Diet
PubMed: 34402657
DOI: 10.1080/10408398.2021.1963208 -
Scientific Reports Jul 2022Skin ageing is the result of intrinsic genetic and extrinsic lifestyle factors. However, there is no consensus on skin ageing phenotypes and ways to quantify them. In...
Skin ageing is the result of intrinsic genetic and extrinsic lifestyle factors. However, there is no consensus on skin ageing phenotypes and ways to quantify them. In this systematic review, we first carefully identified 56 skin ageing phenotypes from multiple literature sources and sought the best photo-numeric grading scales to evaluate them. Next, we conducted a systematic review on all 44 Genome-wide Association Studies (GWAS) on skin ageing published to date and identified genetic risk factors (2349 SNPs and 366 genes) associated with skin ageing. We identified 19 promising SNPs found to be significantly (p-Value < 1E-05) associated with skin ageing phenotypes in two or more independent studies. Here we show, using enrichment analyses strategies and gene expression data, that (1) pleiotropy is a recurring theme among skin ageing genes, (2) SNPs associated with skin ageing phenotypes are mostly located in a small handful of 44 pleiotropic and hub genes (mostly on the chromosome band 16q24.3) and 32 skin colour genes. Since numerous genes on the chromosome band 16q24.3 and skin colour genes show pleiotropy, we propose that (1) genes traditionally identified to contribute to skin colour have more than just skin pigmentation roles, and (2) further progress towards understand the development of skin pigmentation requires understanding the contributions of genes on the chromosomal band 16q24.3. We anticipate our systematic review to serve as a hub to locate primary literature sources pertaining to the genetics of skin ageing and to be a starting point for more sophisticated work examining pleiotropic genes, hub genes, and skin ageing phenotypes.
Topics: Genetic Pleiotropy; Genome-Wide Association Study; Phenotype; Polymorphism, Single Nucleotide; Skin Aging
PubMed: 35907981
DOI: 10.1038/s41598-022-17443-1 -
JAMA Dermatology Sep 2021Dermoscopy increases the diagnostic accuracy for melanoma. However, the accuracy of individual structures and patterns used in melanoma detection has not been... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Dermoscopy increases the diagnostic accuracy for melanoma. However, the accuracy of individual structures and patterns used in melanoma detection has not been systematically evaluated.
OBJECTIVE
To assess the diagnostic accuracy of individual dermoscopic structures and patterns used in melanoma detection.
DATA SOURCES
A search of Ovid Medline, Embase, Cochrane CENTRAL, Scopus, and Web of Science was conducted from inception to July 2020.
STUDY SELECTION
Studies evaluating the dermoscopic structures and patterns among melanomas in comparison with nonmelanoma lesions were included. Excluded were studies with fewer than 3 patients, studies in languages other than English or Spanish, studies not reporting dermoscopic structures per lesion type, and studies assessing only nail, mucosal, acral, facial, or metastatic melanomas or melanomas on chronically sun-damaged skin. Multiple reviewers applied these criteria, and 0.7% of studies met selection criteria.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline and Meta-analysis of Observational Studies in Epidemiology reporting guideline were followed. Guidelines were applied via independent extraction by multiple observers. Data were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
The prespecified outcome measures were diagnostic accuracy (sensitivity and specificity) and risk (odds ratio [OR]) of melanoma for the following dermoscopic structures/patterns: atypical dots/globules, atypical network, blue-white veil, negative network, off-centered blotch, peripheral-tan structureless areas, atypical vessels (eg, linear irregular, polymorphous), pseudopods, streaks, regression (ie, peppering, scarlike areas), shiny white structures, angulated lines, irregular pigmentation, and a multicomponent pattern.
RESULTS
A total of 40 studies including 22 796 skin lesions and 5736 melanomas were evaluated. The structures and patterns with the highest ORs were shiny white structures (OR, 6.7; 95% CI, 2.5-17.9), pseudopods (OR, 6.7; 95% CI, 2.7-16.1), irregular pigmentation (OR, 6.4; 95% CI, 2.0-20.5), blue-white veil (OR, 6.3; 95% CI, 3.7-10.7), and peppering (OR, 6.3; 95% CI, 2.4-16.1). The structures with the highest specificity were pseudopods (97.3%; 95% CI, 94.3%-98.7%), shiny white structures (93.6%; 95% CI, 85.6%-97.3%), peppering (93.4%; 95% CI, 81.9%-97.8%), and streaks (92.1%; 95% CI, 88.4%-94.7%), whereas features with the highest sensitivity were irregular pigmentation (62.3%; 95% CI, 31.2%-85.8%), blue-white veil (60.6%; 95% CI, 46.7%-72.9%), atypical network (56.8%; 95% CI, 43.6%-69.2%), and a multicomponent pattern (53.7%; 95% CI, 40.4%-66.4%).
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis support the diagnostic importance of dermoscopic structures associated with melanoma detection (eg, shiny white structures, blue-white veil), further corroborate the importance of the overall pattern, and may suggest a hierarchy in the significance of these structures and patterns.
Topics: Dermoscopy; Humans; Melanoma; Pigmentation Disorders; Retrospective Studies; Skin Diseases; Skin Neoplasms
PubMed: 34347005
DOI: 10.1001/jamadermatol.2021.2845