High-Intensity, High-Frequency, Parallel Ultrasound Beams for Cellulite of the Buttocks and Thighs.

BACKGROUND: Ultrasound energy can successfully treat fine lines and wrinkles, as well as lift the eyebrow and submentum. Ultrasound waves of high intensity induce thermal injury in the dermis with subsequent tissue remodeling. OBJECTIVE: To examine the utility of a novel ultrasound device that utilizes high-intensity, high-frequency, parallel ultrasound beams to improve the clinical appearance of cellulite on the thighs and buttocks. MATERIALS AND METHODS: A prospective, multicenter, clinical study investigated this novel ultrasound device using 2 treatments. RESULTS: Sixty-five subjects completed both treatments. The mean age was 46 years, and 100% were women. Fitzpatrick skin types I to VI were represented. Assessments compared 3-month follow-up with baseline. Two blinded reviewers agreed in identifying pretreatment and post-treatment photographs for 89.2%. For Cellulite Severity Scale rating, there was significant improvement of 1.61 units (p < .001). For cellulite Global Aesthetic Improvement Scale (GAIS), 89.2% had improvement, with a mean of 0.87 units (p < .001). For Laxity Scale rating, there was significant improvement of 0.70 units (p < .001). For skin laxity GAIS, 89.2% had improvement, with a mean of 0.76 units (p < .001). No device-related adverse events occurred. CONCLUSION: A novel ultrasound device that utilizes high-intensity, high-frequency, parallel ultrasound beams can safely and effectively improve the clinical appearance of cellulite on the thighs and buttocks.

Artificial Intelligence in Dermatology: A Systematic Review of Its Applications in Melanoma and Keratinocyte Carcinoma Diagnosis.

BACKGROUND: Limited access to dermatologic care may pose an obstacle to the early detection and intervention of cutaneous malignancies. The role of artificial intelligence (AI) in skin cancer diagnosis may alleviate potential care gaps. OBJECTIVE: The aim of this systematic review was to offer an in-depth exploration of published AI algorithms trained on dermoscopic and macroscopic clinical images for the diagnosis of melanoma, basal cell carcinoma, and cutaneous squamous cell carcinoma (cSCC). METHODS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted on peer-reviewed articles published between January 1, 2000, and January 26, 2023. RESULTS AND DISCUSSION: Among the 232 studies in this review, the overall accuracy, sensitivity, and specificity of AI for tumor detection averaged 90%, 87%, and 91%, respectively. Model performance improved with time. Despite seemingly impressive performance, the paucity of external validation and limited representation of cSCC and skin of color in the data sets limits the generalizability of the current models. In addition, dermatologists coauthored only 12.9% of all studies included in the review. Moving forward, it is imperative to prioritize robustness in data reporting, inclusivity in data collection, and interdisciplinary collaboration to ensure the development of equitable and effective AI tools.

High-volume facilities are significantly more likely to use guideline-adherent systemic immunotherapy for metastatic Merkel cell carcinoma: implications for cancer care regionalization.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high rate of mortality. While still relatively rare, the incidence of MCC has been rapidly rising in the US and around the world. Since 2017, two immunotherapeutic drugs, avelumab and pembrolizumab, have been FDA-approved for the treatment of metastatic MCC and have revolutionized outcomes for MCC. However, real-world outcomes can differ from clinical trial data, and the adoption of novel therapeutics can be gradual. We aimed to characterize the treatment practices and outcomes of patients with metastatic MCC across the US. A retrospective cohort study of adult cases of MCC in the National Cancer Database diagnosed from 2004 to 2019 was performed. Multivariable logistic regressions to determine the association of a variety of patient, tumor, and system factors with likelihood of receipt of systemic therapies were performed. Univariate Kaplan-Meier and multivariable Cox survival regressions were performed. We identified 1017 cases of metastatic MCC. From 2017 to 2019, 54.2% of patients received immunotherapy. This increased from 45.1% in 2017 to 63.0% in 2019. High-volume centers were significantly more likely to use immunotherapy (odds ratio 3.235, p = 0.002). On univariate analysis, patients receiving systemic immunotherapy had significantly improved overall survival (p < 0.001). One-, 3-, and 5-year survival was 47.2% (standard error [SE] 1.8%), 21.8% (SE 1.5%), and 16.5% (SE 1.4%), respectively, for patients who did not receive immunotherapy versus 62.7% (SE 3.5%), 34.4% (SE 3.9%), and 23.6% (SE 4.4%), respectively, for those who did (Fig. 1). In our multivariable survival regression, receipt of immunotherapy was associated with an approximately 35% reduction in hazard of death (hazard ratio 0.665, p < 0.001; 95% CI 0.548-0.808). Our results demonstrate that the real-world survival advantage of immunotherapy for metastatic MCC is similar to clinical trial data. However, many patients with metastatic disease did not receive this guideline-recommended therapy in our most recent study year, and use of immunotherapy is higher at high-volume centers. This suggests that regionalization of care to high-volume centers or dissemination of their practices, may ultimately improve patient survival.

Laser Removal of Eyeliner and Eyebrow Tattoos: Chart Review, Experiences, and Learnings.

Background: Cosmetic tattoos in the periocular area, including microblading, have become increasingly popular. More patients have been seeking laser tattoo removal.OBJECTIVE: A retrospective chart review for the laser treatment of eyeliner and eyebrow tattoos and a discussion of treatment experiences can better inform physicians. Methods: A retrospective chart review was performed over five years with patients who had eyeliner and/or eyebrow tattoos and had laser removal. Results: Overall, 76 patients were treated. Mean age was 47 years, and 98.7 percent were women. Fitzpatrick Skin Types I-VI were represented. Of all cases, 55.3 percent included eyebrows, 43.4 percent eyelids, and 1.3 percent both. There was a mean of 2.8 treatments. Common colors included black (73.7%), black/red (7.9%), black/orange (5.3%), black/yellow (3.9%), and red (3.9%). Most cases were treated with 755nm picosecond laser or high peak-powered 532nm/1064nm picosecond laser. After initial treatment, 26.3 percent of cases involved unmasking of colors, such as red, orange, yellow, green, and blue, which were not previously visualized. There were no documented adverse events related to scarring, hypotrichosis, necrosis, and burns. Conclusion: Laser removal of eyeliner and eyebrow tattoos can be safe and effective. There should be consideration for eye and hair protection, pain control, and pigment unmasking.

Metabolomic Profiles of Human Glioma Inform Patient Survival.

Aims: Targeting tumor metabolism may improve the outcomes for patients with glioblastoma (GBM). To further preclinical efforts targeting metabolism in GBM, we tested the hypothesis that brain tumors can be stratified into distinct metabolic groups with different patient outcomes. Therefore, to determine if tumor metabolites relate to patient survival, we profiled the metabolomes of human gliomas and correlated metabolic information with clinical data. Results: We found that isocitrate dehydrogenase-wildtype (IDHwt) GBMs are metabolically distinguishable from IDH mutated (IDHmut) astrocytomas and oligodendrogliomas. Survival of patients with IDHmut gliomas was expectedly more favorable than those with IDHwt GBM, and metabolic signatures can stratify IDHwt GBMs subtypes with varying prognoses. Patients whose GBMs were enriched in amino acids had improved survival, while those whose tumors were enriched for nucleotides, redox molecules, and lipid metabolites fared more poorly. These findings were recapitulated in validation cohorts using both metabolomic and transcriptomic data. Innovation: Our results suggest the existence of metabolic subtypes of GBM with differing prognoses, and further support the concept that metabolism may drive the aggressiveness of human gliomas. Conclusions: Our data show that metabolic signatures of human gliomas can inform patient survival. These findings may be used clinically to tailor novel metabolically targeted agents for GBM patients with different metabolic phenotypes. Antioxid. Redox Signal. 39, 942-956.

Predictors of large cell transformation in patients with Sezary Syndrome-A retrospective analysis.

BACKGROUND: Large cell transformation (LCT) of Sezary Syndrome (SS) is a rare phenomenon. To date, there are no rigorous studies identifying risk factors for its development. OBJECTIVES: Here, we seek to characterize the clinicopathologic risk factors that predispose patients with SS to develop LCT. METHODS: We retrospectively evaluated all SS patient records available in the Michigan Medicine Cancer Registry from 2010-2021. Clinical and pathologic variables were compared between groups. The Kaplan-Meier method and log-rank test were used to assess overall survival. RESULTS: Of 28 SS patients identified, eight patients experienced LCT, and 20 did not (NLCT). Peak lactate dehydrogenase (LDH) before LCT (p = 0.0012), maximum total body surface area (TBSA) involvement before LCT (p = 0.0114), absolute CD8+ cell count measured on flow cytometry at diagnosis of SS (p = 0.0455) and at the most recent blood draw (p = 0.00736), and ulceration on biopsy (p = 0.0034) were significant clinicopathologic variables identified between the SS patients that developed LCT versus those that did not. CONCLUSIONS: Maximum TBSA involvement, peak LDH, presence of ulceration, and decreased levels of CD8+ cells in the peripheral blood may predict the development of LCT in patients with SS.

Intra- and post-operative risk of retinal breaks during vitrectomy for macular hole and vitreomacular traction.

BACKGROUND/OBJECTIVE: To evaluate the development of intra- and post-operative retinal breaks after pars plana vitrectomy (PPV) for macular hole (MH) and/or vitreomacular traction (VMT). SUBJECTS/METHODS: Medical records of patients who underwent PPV at Kellogg Eye Center between 1/1/2005-6/30/2018, were evaluated in three groups: group 1, MH/VMT (n = 136); group 2, epiretinal membrane (ERM) without VMT (n = 270); and group 3, diagnostic vitrectomy (DV) or vitreous opacities (n = 35). Statistical analyses were conducted using SAS. RESULTS: 20.6% of patients with MH/VMT, 8.5% of patients with ERM, and 5.7% of patients with DV or vitreous opacities had either intra-operative or post-operative breaks. Indication of MH/VMT versus ERM was a significant predictor for this outcome (p = .0112). The incidence of retinal breaks was higher in operations using 23-gauge versus 25-gauge PPV (25.0% vs. 7.4%, p < .0001). CONCLUSIONS: The presence of MH and/or VMT is a significant risk factor for retinal breaks from PPV, as is use of 23-gauge vitrectomy.

Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis.

BACKGROUND: The international Intermediate Clinical Endpoints in Cancer of the Prostate working group has established metastasis-free survival as a surrogate for overall survival in localised prostate cancer based on the findings of 19 predominantly radiotherapy-based trials. We sought to comprehensively assess aggregate trial-level performance of commonly reported intermediate clinical endpoints across all randomised trials in localised prostate cancer. METHODS: For this meta-analysis, we searched PubMed for all trials in localised or biochemically recurrent prostate cancer published between Jan 1, 1970, and Jan 15, 2020. Eligible trials had to be randomised, therapeutic, reporting overall survival and at least one intermediate clinical endpoint, and with a sample size of at least 70 participants. Trials of metastatic disease were excluded. Intermediate clinical endpoints included biochemical failure, local failure, distant metastases, biochemical failure-free survival, progression-free survival, and metastasis-free survival. Candidacy for surrogacy was assessed using the second condition of the meta-analytical approach (ie, correlation of the treatment effect of the intermediate clinical endpoint and overall survival), using R2 weighted by the inverse variance of the log intermediate clinical endpoint hazard ratio. The intermediate clinical endpoint was deemed to be a surrogate for overall survival if R2 was 0·7 or greater. FINDINGS: 75 trials (53 631 patients) were included in our analysis. Median follow-up was 9·1 years (IQR 5·7-10·6). Biochemical failure (R2 0·38 [95% CI 0·11-0·64]), biochemical failure-free survival (R2 0·12 [0·0030-0·33]), biochemical failure and clinical failure (R2 0·28 [0·0045-0·65]), and local failure (R2 0·085 [0·00-0·37]) correlated poorly with overall survival. Progression-free survival (R2 0·46 [95% CI 0·22-0·67]) showed moderate correlation with overall survival, and metastasis-free survival (R2 0·78 [0·59-0·89]) correlated strongly. INTERPRETATION: Intermediate clinical endpoints based on biochemical and local failure did not meet the second condition of the meta-analytical approach and are not surrogate endpoints for overall survival in localised prostate cancer. Our findings validate metastasis-free survival as the only identified surrogate endpoint for overall survival to date. FUNDING: Prostate Cancer Foundation and National Institutes of Health.

A Systematic Review of the Evidence for the Decipher Genomic Classifier in Prostate Cancer.

CONTEXT: Molecular biomarkers aim to address the established limitations of clinicopathologic factors to accurately risk stratify patients with prostate cancer (PCa). Questions remain as to whether sufficient evidence supports adoption of these biomarkers for clinical use. OBJECTIVE: To perform a systematic review of the available evidence supporting the clinical utility of the Decipher genomic classifier (GC). EVIDENCE ACQUISITION: The review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines by searching PubMed and conference abstracts from January 2010 to June 2020. Evidence was then graded using the criteria of Simon et al (Simon RM, Paik S, Hayes DF. Use of archived specimens in evaluation of prognostic and predictive biomarkers. J Natl Cancer Inst 2009;101:1446-52) and American Urology Association (AUA) criteria. EVIDENCE SYNTHESIS: In total, 42 studies and 30407 patients were included. GC performance data were available for localized, postprostatectomy, nonmetastatic castration-resistant, and metastatic hormone-sensitive PCa as part of retrospective studies (n=12141), prospective registries (n=17053), and prospective and post hoc randomized trial analyses (n=1213). In 32 studies (n=12600), the GC was independently prognostic for all study endpoints (adverse pathology, biochemical failure, metastasis, and cancer-specific and overall survival) on multivariable analysis and improved the discrimination over standard of care in 24 studies (n=8543). GC use changed the management in active surveillance (number needed to test [NNT]=9) and postprostatectomy (NNT=1.5-4) settings in five studies (n=4331). Evidence strength was levels 1 and 2 by the Simon criteria for all disease states other than high-risk PCa, and grades A and B by AUA criteria depending on disease state. CONCLUSIONS: Consistent data are now present from diverse levels of evidence, which when viewed together, have demonstrated clinical utility of the GC in PCa. The utility of the GC is strongest for intermediate-risk PCa and postprostatectomy decision-making. PATIENT SUMMARY: In this paper, we review the evidence of the Decipher genomic classification tool for men with prostate cancer. We found consistent evidence that the test helps identify which cancers are more or less aggressive, which in turn aids in personalized treatment decision-making.

Gianturco Z-stent placement for the treatment of chronic central venous occlusive disease: implantation of 208 stents in 137 symptomatic patients.

PURPOSE: To report the technical successes, adverse events, and long-term stent patency rates of Gianturco Z-stents for management of chronic central venous occlusive disease. METHODS: Overall, 137 patients, with mean age 48.6±16.1 years (range, 16-89 years), underwent placement of Gianturco Z-stents for chronic central venous occlusions. Presenting symptoms included lower extremity edema (n=66, 48.2%), superior vena cava syndrome (n=30, 21.9%), unilateral upper extremity swelling (n=20, 14.6%), hemodialysis fistula or catheter dysfunction (n=11, 8.0%), ascites (n=8, 5.8%), and both ascites and lower extremity edema (n=2, 1.5%). Most common etiologies of central venous occlusion were prior central venous access placement (n=58, 42.3%), extrinsic compression (n=29, 21.2%), and post-surgical anastomotic stenosis (n=27, 19.7%). Number of stents placed, stent implantation location, stent sizes, technical successes, adverse events, need for re-intervention, follow-up evaluation, stent patencies, and mortality were recorded. Technical success was defined as recanalization and stent reconstruction with restoration of in-line venous flow. Adverse events were defined by the Society of Interventional Radiology Adverse Event Classification criteria. Primary and primary-assisted stent patencies were analyzed using Kaplan-Meier analysis. RESULTS: In total, 208 Z-stents were placed. The three most common placement sites were the inferior vena cava (n=124, 59.6%), superior vena cava (n=44, 21.2%), and brachiocephalic veins (n=27, 13.0%). Technical success was achieved in 133 patients (97.1%). There were two (1.5%) severe adverse events (two cases of stent migration to the right atrium), one (0.7%) moderate adverse event, and one (0.7%) mild adverse event. Mean follow-up was 43.6±52.7 months. Estimated 1-, 3-, and 5-year primary stent patency was 84.2%, 84.2%, and 82.1%, respectively. Estimated 1-, 3-, and 5-year primary-assisted patency was 92.3%, 89.6%, and 89.6%, respectively. The 30- and 60- day mortality rates were 2.9% (n=4) and 5.1% (n=7), none of which were directly attributable to Z-stent placement. CONCLUSION: Gianturco Z-stent placement is safe and effective for the treatment for chronic central venous occlusive disease with durable short- and long-term patencies.