Review of Lasers and Energy-Based Devices for Skin Rejuvenation and Scar Treatment With Histologic Correlations.

BACKGROUND: Lasers and energy-based devices (EBD) are popular treatments for skin rejuvenation and resurfacing. Achieving desired outcomes and avoiding complications require understanding the effects of these devices at a histologic level. Currently, no comprehensive review summarizing the histologic effects of laser and energy-based treatments exists. OBJECTIVE: To describe how lasers and EBD alter skin histology and improve the overall understanding of these devices. MATERIALS AND METHODS: A PubMed search was conducted for studies with histologic analysis of fractional picosecond laser, fractional radiofrequency microneedling, nonablative lasers, and ablative lasers. RESULTS: Fractional picosecond lasers induce intraepidermal and/or dermal vacuoles from laser-induced optical breakdown. Fractional radiofrequency microneedling delivers thermal energy to the dermis while sparing the epidermis, making it safer for patients with darker skin phototypes. Fractional nonablative lasers induce conical zones of coagulation of the epidermis and upper dermis. Ablative lasers vaporize the stratum corneum down to the dermis. Traditional ablative lasers cause diffuse vaporization while fractional ablative lasers generate columns of tissue ablation. CONCLUSION: Lasers and EBD are effective for skin resurfacing and rejuvenation and have different mechanisms with disparate targets in the skin. Safe and effective use of devices requires understanding the histologic laser-tissue interaction.

Factors Affecting Depth of Penetration in Microneedling- and Laser-Assisted Drug Delivery: The Importance of Timing of Topical Application.

BACKGROUND: Microneedling- and laser-assisted drug delivery are emerging techniques used to treat various conditions. However, key parameters affecting drug penetration remain unknown. OBJECTIVE: This study aims to investigate the importance of timing of topical application, needle length, and device type for drug delivery. MATERIALS AND METHODS: Skin harvested from cosmetic surgeries was treated with black ink applied before or after treatment with a microneedling pen (MP), roller, or fractional ablative CO2 laser, and incubated for different time intervals. Ink penetration was additionally tested using different needle lengths. Sandwich estimator was used for statistical analysis. RESULTS: Ink applied before MP penetrated deeper compared to ink applied afterward at 1 and 3 hours, and roller microneedling in both the ink-before and -after scenarios at 1, 3, and 6 hours (p < .05). Microneedling demonstrated lateral extension of ink beyond microchannels with increased ink penetration over time. CO2 laser demonstrated ink localization within microthermal zones without time-dependent increases in depth after 30 minutes. Ink penetration increases by 0.06 mm per 1 mm increase in needle length. CONCLUSION: Ink applied before MP results in the deepest penetration of ink. Microneedling offers unique advantages in transdermal delivery as its channels exhibit increasing penetration over time and lateral extension of product.

Botulinum Toxin Injections for Leg Contouring in East Asians.

BACKGROUND: A common aesthetic concern among East Asian women is enlarged calves. Although surgical resection has been a traditional treatment option, botulinum toxin injections into the gastrocnemius muscle are an emerging, noninvasive alternative. OBJECTIVE: To perform a literature review on botulinum toxin injections for leg contouring. MATERIALS AND METHODS: A literature review was conducted using PubMed, Web of Science, Embase, and Cochrane's CENTRAL database to identify articles relating to combinations of the terms botulinum toxin, gastrocnemius, calves, and leg contouring. RESULTS: Based on the limited publications to date, the authors prepared a review on how to treat an enlarged calf with botulinum toxin including injection techniques, anticipated efficacy, outcome monitoring, and potential side effects. CONCLUSION: Botulinum toxin injections for calf reduction are an emerging, noninvasive treatment option. Studies to date suggest that it is an efficacious method with few immediate side effects. Future areas for investigation include defining the criteria for calf hypertrophy, minimum effective dosage of botulinum toxin, and the potential long-term effects of injections.

Characteristics of keratinocyte carcinomas in Hispanics compared to non-Hispanic whites: A retrospective 5-year study.

BACKGROUND: Hispanics are one of the fastest growing populations in the United States. Few studies have characterized the patterns of keratinocyte carcinoma presentation in Hispanics. OBJECTIVE: The study aimed to compare the clinical and histologic characteristics of keratinocyte carcinomas in Hispanics and non-Hispanic whites. MATERIALS AND METHODS: A five-year retrospective chart review was conducted at a single academic center to identify all histologically-confirmed cases of keratinocyte carcinomas. Tumor characteristics were then compared between Hispanics and non-Hispanic whites. RESULTS: A total of 197 tumors were identified of which 76% occurred in non-Hispanic whites and 24% in Hispanics. Tumor diameter was not larger and histologic subtype was not more aggressive in Hispanics compared to non-Hispanic whites. Age of diagnosis of basal cell carcinoma was younger among Hispanics compared to non-Hispanic whites (P < .05). CONCLUSION: Hispanics were not more likely to present with more high-risk keratinocyte carcinomas compared to non-Hispanic whites in terms of tumor diameter, differentiation and subtype.

Botulinum Toxin Injections for Masseter Reduction in East Asians.

BACKGROUND: Cultural ideals for a slimmer face have led to an upsurge in interest in facial contouring among East Asians. Although surgical resection has traditionally been the main treatment option, botulinum toxin injection is becoming a popular, noninvasive alternative. OBJECTIVE: To describe the use of botulinum toxin injection for masseter reduction in East Asians. METHODS: An electronic search of the PubMed database was performed for studies published from 2000 to 2017 that meet the word combination of botulinum toxin, masseter, hypertrophy, and/or lower face contouring. Only the studies conducted in East Asian countries were analyzed in this review, exception of one study from Thailand. RESULTS: A total of 12 publications were identified. Each study was reviewed to extract relevant information on patient selection, injection techniques, efficacy, dosage, frequency, and main side effects of treating masseters with botulinum toxin. CONCLUSION: Botulinum toxin injection for masseter reduction in East Asians is efficacious and generally considered safe with no significant side effects. Future areas for investigation include defining the criteria for benign masseteric hypertrophy, minimum effective dosage of botulinum toxin, and the potential long-term effects of the injection.

Appearance-based vs health-based sun protective messages: A randomized, double-blind controlled study.

BACKGROUND: Appearance-based messages have shown promise in improving sun protection habits among Caucasians but have scarcely been investigated in Hispanic populations. OBJECTIVE: To compare the effectiveness of appearance-based vs health-based messages in an ethnic patient population, where hyperpigmentation disorders are prevalent and often cosmetically concerning. METHODS: One hundred thirty-seven patients were randomized to receive images of (a) skin cancer, (b) hyperpigmentation, or (c) wrinkles. Analysis of variance tests for repeated measures were used to estimate the effects of the different stimuli on participants' knowledge and intention to sun protect. RESULTS: Appearance-based interventions were more effective in improving intentions to sun protect among both Hispanics and non-Hispanic Whites (P < 0.05). They were furthermore more effective among younger patient populations (≤40 years old) and patients who thought that a tanned appearance is attractive (P < 0.05). CONCLUSIONS: Appearance-based photos of sun damage were more effective than health-based messages among Hispanics, younger patient populations, and those who find tanned appearances to be attractive.

Prognostic variables in high-risk cutaneous squamous cell carcinoma: a review.

Cutaneous squamous cell carcinoma (SCC) is a growing public health problem in the United States. A subset of high-risk SCC exhibits a more aggressive clinical trajectory including increased local recurrence and lymph node metastasis. However, there are no universally accepted criteria to help define and manage these patients. This review provides an overview of the high-risk features of cutaneous SCC, prognostic stratification of various staging systems and treatment options. It further examines the prognostic factors influencing the staging of cutaneous head and neck SCC.

History of allergy and atopic dermatitis in relation to squamous cell and Basal cell carcinoma of the skin.

BACKGROUND: Little is known about whether history of allergies and atopy is related to the occurrence of keratinocyte cancers. Thus, we evaluated the association between history of allergies and atopy and the incidence of squamous cell carcinoma (SCC) and early onset basal cell carcinoma (BCC). METHODS: As part of a population-based case-control study, interviews were conducted with 1,050 residents of New Hampshire (375 early onset BCC cases and 251 controls, 254 SCC cases and 432 controls). ORs of SCC and early onset BCC and history of allergy and atopic dermatitis were computed using logistic regression, while controlling for potential confounding factors. RESULTS: An overall inverse association was observed between a history of allergy and early onset BCC [OR, 0.61; 95% confidence interval (CI), 0.38-0.97] but not SCC (OR, 1.18; 95% CI, 0.78-1.79). Among women, we found reduced ORs of both early onset BCC and of SCC in relation to allergy history (early onset BCC OR, 0.53; 95% CI, 0.31-0.92 and SCC OR, 0.59; 95% CI, 0.29-1.19). Among men, we observed no clear association with early onset BCC (OR, 0.87; 95% CI, 0.39-1.99) and an increased risk of SCC (OR, 1.58; 95% CI, 0.93-2.69). CONCLUSION: Our findings suggest that allergies and atopy may influence risk of early onset BCC and SCC, and that effects may be gender specific. IMPACT: A deeper understanding of the immune mechanisms underlying allergies and atopy may provide new routes of preventing keratinocyte cancers.

Ticagrelor: oral reversible P2Y(12) receptor antagonist for the management of acute coronary syndromes.

BACKGROUND: The clinical benefits of dual antiplatelet treatment (aspirin + clopidogrel) in the management of acute coronary syndromes (ACS) are well established. However, clopidogrel is a prodrug that requires hepatic activation. Concerns regarding its delayed onset of action, variability in antiplatelet effects, and prolonged recovery of platelet function after discontinuation have prompted the development of P2Y(12) receptor antagonists. Ticagrelor is the most recently developed P2Y(12) receptor antagonist available in the United States. Ticagrelor is a nonthienopyridine antiplatelet agent and is the first reversible oral antagonist of the P2Y(12) receptors. OBJECTIVE: This article reviews the pharmacology, clinical efficacy, and tolerability of ticagrelor use in management of ACS. METHODS: Peer-reviewed clinical trials, review articles, and relevant treatment guidelines published from 1966 to March 15, 2012, were identified from the MEDLINE and Current Content databases using the search terms ticagrelor, ACS, pharmacokinetics, pharmacodynamics, pharmacoeconomics, and cost-effectiveness. Citations from available articles were also reviewed for additional references. RESULTS: Nine pharmacokinetics/pharmacodynamics studies in humans and 1 clinical study were identified. In addition, the findings from 6 subanalyses based on the clinical study were included. Compared with clopidogrel, ticagrelor was associated with a significantly reduced composite rate of death from cardiovascular causes, myocardial infarction, or stroke (ticagrelor, 9.8%; clopidogrel, 11.7%; hazard ratio [HR] = 0.84; 95% CI, 0.77-0.92; P < 0.001). The difference in the rates of major bleeding was not significant (ticagrelor, 11.6%; clopidogrel, 11.2%). Ticagrelor was associated with a higher rate of non-coronary artery bypass graft surgery related major bleeding (4.5% vs 3.8%; P = 0.03), including fatal intracranial bleeding (0.1% vs 0.01%; P = 0.02), and fewer cases of other types of fatal bleeding (0.1% vs 0.3%; P = 0.03). Other adverse events reported with ticagrelor use included dyspnea (13.8%), headache (6.5%), and bradyarrhythmia (5.8%). The effects of ticagrelor have not been compared to those of other antiplatelet agents, including prasugrel. CONCLUSIONS: Based on the findings from the present review, ticagrelor provides reversible inhibition of adenosine diphosphate-induced platelet aggregation, with a faster onset of action than clopidogrel, and is effective in the treatment of patients with ACS. More data are required to definitively position ticagrelor with respect to other antiplatelet agents, including prasugrel.

Engineering of targeted nanoparticles for cancer therapy using internalizing aptamers isolated by cell-uptake selection.

One of the major challenges in the development of targeted nanoparticles (NPs) for cancer therapy is to discover targeting ligands that allow for differential binding and uptake by the target cancer cells. Using prostate cancer (PCa) as a model disease, we developed a cell-uptake selection strategy to isolate PCa-specific internalizing 2'-O-methyl RNA aptamers (Apts) for NP incorporation. Twelve cycles of selection and counter-selection were done to obtain a panel of internalizing Apts, which can distinguish PCa cells from nonprostate and normal prostate cells. After Apt characterization, size minimization, and conjugation of the Apts with fluorescently labeled polymeric NPs, the NP-Apt conjugates exhibit PCa specificity and enhancement in cellular uptake when compared to nontargeted NPs lacking the internalizing Apts. Furthermore, when docetaxel, a chemotherapeutic agent used for the treatment of PCa, was encapsulated within the NP-Apt, a significant improvement in cytotoxicity was achieved in targeted PCa cells. Rather than isolating high-affinity Apts as reported in previous selection processes, our selection strategy was designed to enrich cancer cell-specific internalizing Apts. A similar cell-uptake selection strategy may be used to develop specific internalizing ligands for a myriad of other diseases and can potentially facilitate delivering various molecules, including drugs and siRNAs, into target cells.

Rosuvastatin in the management of hyperlipidemia.

BACKGROUND: Rosuvastatin is a new statin indicated to reduce elevated levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides and to increase levels of high-density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia, mixed dyslipidemia, and homozygous familial hypercholesterolemia. OBJECTIVE: The purpose of this article was to review the pharmacology, clinical efficacy, and tolerability of rosuvastatin as monotherapy and combination therapy for patients with hyperlipidemia. METHODS: A literature review was conducted using the search term rosuvastatin to identify English-language peer-reviewed articles and abstracts in the MEDLINE and Current Contents databases (both 1966 to March 2004). Citations from available articles were reviewed for additional references, and selected information from the manufacturer was discussed. RESULTS: Rosuvastatin 10 to 40 mg/d reduced LDL-C by 43% to 63% (P < 0.05). Compared with other statins, rosuvastatin had the highest dose-to-dose potency in lowering LDL-C (reduction of 60% vs 50% with atorvastatin, 40% with simvastatin, 30% with pravastatin or lovastatin, and 20% with fluvastatin) and better efficacy in raising HDL-C (increase of approximately 10% vs approximately 5% with other statins; P < 0.05). Rosuvastatin enabled significantly more patients to achieve the National Cholesterol Education Program (NCEP) goals for LDL-C with lower doses (P < 0.05). Rosuvastatin was well tolerated. Incidences of myopathy and liver function test abnormalities were rare and comparable to those of other statins. Because it is not metabolized by the cytochrome P-450 enzymes, rosuvastatin had fewer clinically significant drug interactions compared with other statins. Studies to assess the effect of rosuvastatin on cardiovascular outcomes are ongoing. CONCLUSIONS: Clinical studies continue to demonstrate that achieving optimal levels of LDL-C is an important goal in reducing cardiovascular events. Recent evidence suggests the need for an even lower LDL-C goal than that being recommended by the NCEP Based on the studies included in this review, rosuvastatin may help patients achieve optimal goals early with lower dosages, thus reducing the need for dose titration or combination therapy.

Use of erythropoietin in heart failure management.

OBJECTIVE: To review the use of erythropoietin for anemia in heart failure (HF). DATA SOURCES: Peer-reviewed articles in MEDLINE (1966-June 2004) were identified and citations from available articles were reviewed using the search terms anemia, erythropoietin, and heart failure. DATA SYNTHESIS: Anemia worsens HF prognosis. Clinical studies in patients with New York Heart Association Class III/IV HF who had hemoglobin <12 mg/dL and were refractory to maximal medical management showed that erythropoietin improves symptoms. Larger scale studies with mortality endpoints are required to confirm the benefits. CONCLUSIONS: In selected patients with severe, chronic HF, erythropoietin may be considered for functional improvement. However, routine use of this treatment strategy is not recommended until more data are available.

Early experiences and clinical implications of restenosis and drug-eluting stents: Part 2.

OBJECTIVE: To review early clinical experience and future implications of drug-eluting stents (DES) in percutaneous coronary interventions. DATA SOURCES: Using the search terms sirolimus, paclitaxel, and drug-eluting stents, a literature review was conducted to identify peer-reviewed articles and abstracts in MEDLINE (1966-June 2003). Recent meeting abstracts were also accessed through the American Heart Association and the American College of Cardiology Web sites. Citations from available articles were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: Published reviews and studies showing the effects of in-stent restenosis and drug-coated and -eluting stents were evaluated and reviewed. DATA SYNTHESIS: Current antiplatelet and antithrombotic therapy have proven successful in preventing acute in-stent thrombosis, but not in-stent restenosis. Recently, stents eluted with certain antimitotic agents have demonstrated positive findings in reducing restenosis (eg, sirolimus, paclitaxel-eluting stents) compared with bare-metal stents. However, data regarding long-term benefits and adverse effects are only beginning to accumulate. CONCLUSIONS: While the current clinical efficacy and safety of DES appear promising, further investigations are required to examine long-term efficacy, safety, and cost-effectiveness. Subanalysis of the current data may help to determine the specific patient population that may benefit maximally from DES.

Fondaparinux: a new antithrombotic agent.

BACKGROUND: Venous thrombosis is usually triggered by a low-flow state, as in prolonged periods of bed rest after hip or knee surgery. Antithrombotic agents are the drugs of choice in such circumstances. The new factor Xa inhibitor fondaparinux has been approved by the US Food and Drug Administration for the prevention of venous thromboembolism in patients undergoing hip fracture surgery, hip replacement surgery, or knee replacement surgery. OBJECTIVE: The aim of this article was to review the clinical pharmacology of fondaparinux and summarize the data from available clinical trials of this agent. METHODS: The terms fondaparinux, SR90107A/ORG31540, and factor Xa were used to search MEDLINE and Current Contents/Clinical Medicine for English-language studies in humans published between 1996 and May 2002. Unpublished data were provided by the manufacturer of fondaparinux, and additional information was obtained from abstracts presented at the 2001 congress of the International Society on Thrombosis and Haemostasis in Paris. RESULTS: Fondaparinux is a synthetic pentasaccharide that selectively binds to antithrombin III, inducing a conformational change that increases anti-factor Xa activity. Phase III studies to date have reported that fondaparinux had greater efficacy compared with enoxaparin in terms of prevention of venous thromboembolism after hip or knee replacement surgery. Preliminary studies have suggested that this agent may have efficacy in the treatment of deep vein thrombosis, as well as in the management of acute coronary syndromes. However, 1 study reported a significant increase in the risk of major bleeding with fondaparinux compared with enoxaparin (2.1% vs 0.2%, respectively; P = 0.006), and another reported a significant increase in the risk of minor bleeding (4.1% vs 2.1%; P = 0.02). CONCLUSIONS: Fondaparinux has shown efficacy in the prevention of venous thromboembolism in patients undergoing hip or knee replacement surgery. Large-scale clinical trials of its potential efficacy in deep vein thrombosis and acute coronary syndromes are ongoing. Use of fondaparinux may be associated with an increased bleeding risk, and patients should be assessed individually to ensure that the possible benefits outweigh the risks. Routine use of fondaparinux as a replacement for low-molecular-weight heparin is not recommended at this time.

Efficacy of glycoprotein IIb/IIIa-receptor inhibitors during percutaneous coronary intervention.

The clinical efficacy of glycoprotein (GP) IIb/IIIa-receptor inhibitors is discussed. Over the past 10 years, GP IIb/IIIa-receptor inhibitors have become the standard of care for patients undergoing percutaneous coronary intervention (PCI). Abciximab, a monoclonal antibody fragment inhibitor of GP IIb/IIIa receptors, has been found to significantly reduce the frequency of death or myocardial infarction in patients undergoing PCI in several large trials. Board use of abciximab for this indication was precluded by the high cost of this agent. Significant benefits of the small-molecule GP IIb/IIIa-receptor inhibitor epitifibatide in patients undergoing PCI led to substantially greater use of GP IIb/IIIa-receptor inhibitors in these patients because of the considerably lower cost of this agent. Positive results of trials of abciximab and eptifibatide in patients receiving PCI can be attributed to the fact that the dosage regimens of these agents in large trials consistently inhibited > 80% of platelet aggregation, particularly during the critical periprocedural period. In contrast, the nonpeptide GP IIb/IIIa-receptor inhibitor tirofiban yielded negative results in two large trials, probably because of < 80% inhibition of platelet aggregation with the dosage regimen used, especially during the first hour of therapy when PCI is performed. Large clinical trials strongly support the use of abciximab or eptifibatide, but not tirofiban, in patients undergoing PCI.

Tacrolimus in cardiac transplantation: efficacy and safety of a novel dosing protocol.

BACKGROUND: Although used for more than 20 years, optimal dosing strategies of most immunosuppressants have never been determined. Tacrolimus, one of the newer agents used in solid-organ transplantation, is gaining increasing popularity because of its ability to reverse refractory rejection in cyclosporine-treated patients and its favorable side-effect profile. As with many other immunosuppressive agents, absorption and metabolism vary between individuals, which complicates dosing. METHODS: We hypothesized that a 1-mg dose of tacrolimus may be used to gauge each patient's metabolism. A novel dosing scheme was evaluated to establish the safety and efficacy of this approach. Outcomes were incidence of renal insufficiency and treatment efficacy as assessed by the rejection grade on the first endomyocardial biopsy. RESULTS: The risk of renal insufficiency was low, with only a 3% rise in creatinine at 7 days posttransplant. The risk of renal insufficiency was highest during the first 3 days of tacrolimus therapy, and the change in tacrolimus level during this time was identified as the single best predictor of renal insufficiency. From days 4 to 7, the rise in tacrolimus level had much less influence on renal function. Ninety-two percent of patients had a low- or intermediate-grade first cardiac biopsy. CONCLUSIONS: It was shown that this conservative initial dosing approach, which guarantees renal safety, is not associated with an increased risk of allograft rejection. We conclude that administration of tacrolimus via a tailored protocol soon after transplantation ensures a safe and effective means of immunosuppression.