Infantile hemangiomas: what have we learned from propranolol?

PURPOSE OF REVIEW: Infantile hemangiomas are the most common vascular tumor of infancy. Treatment of infantile hemangiomas was revolutionized when propranolol, a nonselective ß-blocker, was reported to be effective therapy. In this review, we highlight the lessons learned using propranolol to treat infantile hemangiomas. We also describe the ongoing effort to understand the mechanism of action of propranolol. RECENT FINDINGS: Although the pathogenesis of infantile hemangiomas is not fully understood, maternal hypoxic stress and embolization of placental tissue are suggested to be critical components in their development. The mechanism of action of propranolol remains unclear, however various molecular mechanisms are detailed in this review. Propranolol treatment remains a well tolerated therapy, with low risk of adverse events or long-term neurocognitive effects. Dosing recommendations and optimal treatment duration vary among studies, and should be altered in patients with certain medical conditions such as Posterior fossa anomalies, Hemangioma, Arterial lesions, Cardiac abnormalities/coarctation of the aorta, Eye anomalies (PHACE) syndrome. SUMMARY: Propranolol is a well tolerated and effective treatment for infantile hemangiomas. The efficacy of propranolol for infantile hemangiomas is clear, however questions pertaining to mechanism of action, pretreatment risk stratification, and optimal dosing remain unanswered. The guidelines for managing infantile hemangiomas with propranolol will continue to adapt as research catches up to clinical experience.

Underutilization of Mohs Micrographic Surgery for Less Common Cutaneous Malignancies in the United States.

BACKGROUND: Consensus guidelines have defined select less common skin cancers appropriate for Mohs micrographic surgery (MMS), as these tumors are characterized by asymmetric growth patterns that challenge conventional surgical extirpation of disease. OBJECTIVE: The authors aimed to define surgical patterns of care and to identify factors affecting treatment selection in the United States. MATERIALS AND METHODS: Retrospective cohort analysis of nonmetastatic nonmelanoma skin cancers deemed appropriate for MMS by American Academy of Dermatology/American College of Mohs Surgery/American Society for Dermatologic Surgery Association/American Society for Mohs Surgery appropriate use criteria from the National Cancer Data Base from 1998 to 2012. RESULTS: Of the included 15,121 patients, 8% received MMS, 30% primary excision, 12% narrow re-excision, and 50% wide re-excision. Utilization of MMS was negatively influenced by community cancer programs, Northeast region, lower education, uninsured status, and administration of radiotherapy. High-risk face areas, lower comorbidity score, and microcystic adnexal carcinoma were associated with higher likelihood of receiving MMS. After adjusting for tumor size, tumor location, and histology, MMS remained an independent predictor of achieving negative surgical margins (odds ratio 3.15, 95% CI 2.27-4.36, and p < .0001). CONCLUSION: There is considerable variation in surgical treatment patterns by both sociodemographic, treatment, and tumor characteristics. Despite low utilization, patients receiving MMS are more likely to achieve negative surgical margins and less likely to receive radiotherapy.

The Association of Academic Cosmetic Dermatology: improving cosmetic dermatology education through collaboration, research, and advocacy.

Cosmetic and laser procedures are increasingly popular among patients and are skills in which dermatologists are regarded as well trained. Most dermatology residents intend to incorporate cosmetic procedures into their practice and prefer to learn such procedures during residency through direct patient care. However, there are notable challenges in optimizing how residents are trained in cosmetic and laser dermatology. To address these barriers and elevate the practice of cosmetic dermatology in academic medicine, the Association of Academic Cosmetic Dermatology (AACD) was founded in 2021 as the lead professional society for dermatologists who direct the education of resident trainees in cosmetic and laser dermatology. The AACD, a group of board-certified dermatologists who teach cosmetic and laser dermatology to residents, aims to improve cosmetic dermatology education through collaboration, research, and advocacy.

Needs and Gaps in Resident Trainee Education, Clinical Patient Care, and Clinical Research in Cosmetic Dermatology: Position Statement of the Association of Academic Cosmetic Dermatology.

Cosmetic dermatology is a key subspecialty of academic dermatology. As such, academic centers are expected to demonstrate excellence in the teaching of cosmetic dermatology skills to trainees, the clinical delivery of cosmetic dermatology services to patients, and the performance of clinical research that advances knowledge and uncovers new therapies in cosmetic dermatology. The Association of Academic Cosmetic Dermatology (AACD), a newly formed medical professional society, includes as its principal aims the support of all of these areas. AACD is comprised of group of board-certified dermatologists who teach cosmetic and laser dermatology at US dermatology residency programs. An expert panel constituted by the AACD recently convened a workshop to review gaps pertaining to academic cosmetic dermatology. This panel considered needs and potential corrective initiatives in three domains: resident education, patient experience, and clinical research. The work of the panel was used to develop a roadmap, which was adopted by consensus, and which will serve to guide the AACD moving forward.

The effect of a low-nickel diet and nickel sensitization on gastroesophageal reflux disease: A pilot study.

BACKGROUND/AIMS: Gastroesophageal reflux disease (GERD) is a common medical condition, frequently refractory to medical therapy. Nickel is a leading cause of allergic contact dermatitis. Although nickel is widely found in foods, the effect of nickel on GERD is unknown. This pilot study sought to evaluate the effect of a low-nickel diet on GERD and determine if epicutaneous patch testing to nickel could predict responsiveness to a low-nickel diet. METHODS: This prospective, single-site pilot study recruited 20 refractory GERD patients as determined by GERD Health-Related Quality of Life (GERD-HRQL) scores. All patients had epicutaneous patch testing for nickel and were then instructed to follow a low-nickel diet for 8 weeks regardless of patch test results. GERD-HRQL was recorded at baseline and following 8 weeks of a low-nickel diet. Demographic and clinical data associated with GERD and nickel allergy were recorded. A Wilcoxon signed-rank test and nonparametric analysis of longitudinal data were run to determine statistical significance in pre- and post- GERD-HRQL scores in nickel patch test-positive and negative groups. RESULTS: Nearly all (19/20 [95%]) participants reported reduced GERD symptoms after 8 weeks on a low-nickel diet. Mean total GERD-HRQL, regurgitation, and heartburn scores declined (27.05 ± 16.04, 11.45 ± 6.46, 10.85 ± 8.29). Participants with positive vs. negative patch testing to nickel responded equivalently to a low-nickel diet. CONCLUSIONS: A low-nickel diet improves GERD symptoms, but responsiveness to a low-nickel diet does not correlate with epicutaneous patch testing to nickel. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT03720756.

Luminescence experiments involved in the mechanism of streptozotocin diabetes and cataract formation.

Streptozotocin (STZ)-induced diabetes is linked to excessive nitric oxide (NO), and possibly peroxynitrite (OONO(-)) and/or other nitrogen oxides, e.g. nitrogen trioxide (N(2)O(3)), which damages DNA of pancreatic beta cells, causing death and loss of insulin. Simultaneous injection of carboxy-PTIO (CPTIO) and STZ prevents diabetes and cataract formation in rats, whereas 4-hydroxy-Tempo (4HT) does not. CPTIO oxidizes nitric oxide to nitrite, which prevents production of the diabetogenic toxin. Peroxynitrite may not be involved, since 4HT (converts O(2)(-) to H(2)O(2)) injected with STZ produces diabetes. All six of the control rats injected with STZ became diabetic and developed cataracts after 3 months. Eight rats injected with STZ and CPTIO were non-diabetic with no cataracts up to a year. This work establishes the idea that excessive nitric oxide is a primary initiator in STZ diabetes. Luminescence experiments using OONO(-) generation from SIN-1 with L-012 indicates that 4HT is an effective inhibitor, while CPTIO is ineffective. Experiments with dilute solutions of nitrogen trioxide added to ladder or plasmid DNA reveal extensive nicking of DNA, thereby raising the possibility that other oxides of nitrogen could be involved with the damage to DNA. It can be concluded that diabetes can be prevented by oxidizing excessive NO from STZ.

Primary and Radiation-induced Breast Angiosarcoma: Clinicopathologic Predictors of Outcomes and the Impact of Adjuvant Radiation Therapy.

BACKGROUND: Mammary angiosarcoma (AS) is an aggressive malignancy with high recurrence rates and poor overall survival. Limited data exist to guide treatment. We aimed to identify patterns of failure in the context of adjuvant radiation and to identify prognostic indicators to better guide management. METHODS: Thirty-five patients with breast AS at UPMC Magee Women's Hospital from June 1994 to March 2011 were retrospectively reviewed. Pathology was rereviewed for 22 patients by an expert breast pathologist using an objective scoring system, partly based on the Rosen grading scheme. All patients completed R0 resection, with 14 of them receiving adjuvant radiotherapy (RT) (82% of which represented reirradiation for radiation-induced AS). RESULTS: At a median follow-up of 20 months (range, 3 to 178 mo), the primary mode of failure was local with 32% local first failure. Tumor size >5 cm, radiation-induced etiology, and the omission of adjuvant RT were important prognostic factors of tumor control and survival. Histopathology including necrosis, number of mitotic figures, endothelial tufting, solid/spindle cell foci, and the combined scoring system were prognostic for recurrence patterns. CONCLUSIONS: Breast AS has high rates of local failure despite R0 resection, which may be improved with adjuvant RT, even in the reirradiation setting. Histopathology is prognostic for recurrence patterns.

Can diabetes I and early blindness be prevented using a tylenol combination which inhibits oxidative and nitrosative stress?

Since oxidative/nitrosative stress cause diabetes, can we prevent this chemistry generating the disease? Streptozotocin causes diabetes by entering the pancreatic beta cell generating excessive nitric oxide which reacts with oxygen creating a toxin possibly peroxynitrite, dinitrogen trioxide, dinitrogen tetraoxide and so forth. The toxic compounds damage the DNA causing beta cell death. This prevents insulin synthesis, storage and release. By using antioxidant substances that destroy the nitric-oxide-based toxins (e.g., carboxy-PTIO (oxidizes nitric oxide), polyphenolic-quercetin and monophenolic acetaminophen (Tylenol)) which are oxidation and nitration targets can the diabetes I causing toxins in animals be destroyed? Will this tri-drug combination completely prevent the deleterious effects of diabetes namely poor blood glucose control and blindness from cataracts for the entire length of the experiment (one year). These disease reversal experiments were accomplished in rats where the streptozotocin-diabetic effects were completely thwarted. In vitro experiments were accomplished to provide the scientific basis for the experimental results in animals.

Ultrasensitive peroxynitrite-based luminescence with L-012 as a screening system for antioxidative/antinitrating substances, e.g. Tylenol (acetaminophen), 4-OH tempol, quercetin and carboxy-PTIO.

Previously our group developed a water-soluble antioxidant screening system using the luminescence of the reaction of peroxynitrite and luminol. In the present study we replaced luminol with the luminol-like compound L-012. This increases the production of luminescence approximately 100-fold and therefore, with a higher signal:noise ratio, this new system can detect antioxidation and antinitration effects at lower doses of the inhibitor. We studied acetaminophen (Tylenol) and its metabolite 3-nitroacetaminophen, tyrosine and nitrotyrosine and all these substances were inhibitory in a dose-responsive manner and below micromolar amounts. In addition quercetin, a polyphenol, was highly active (below micromolar amounts) as an antioxidant and antinitrating compound. 4-OH tempol, the stable free radical, superoxide dismutase (SOD) mimetic, was inhibitory in a dose-responsive manner and below micromolar amounts. Carboxy-PTIO was inhibitory at 10 times micromolar amount but not below that dose, which may be related to colour quenching, since the drug is deeply blue, or possibly it is an inhibitor with a slow kinetic profile. Finally, the amino acid tyrosine has been found to be inhibitory in micromolar amounts, similar to acetaminophen. This indicates that tyrosine can act as an antioxidant and antinitration target alone or conjugated in protein, e.g. insulin.