Split-face histological and biochemical evaluation of tightening efficacy using temperature- and impedance-controlled continuous non-invasive radiofrequency energy.

BACKGROUND: Bipolar radiofrequency (RF) is capable of heating dermal collagen fibers and inducing skin tightening by collagen remodeling. OBJECTIVE: To substantiate safety and improvement of skin laxity following skin heating with a novel temperature- and impedance-controlled non-invasive radiofrequency (RF) device by histological and biochemical evaluations. METHODS: A split-face study was performed on 4 subjects who underwent 8 weekly RF sessions on one side of their face, leaving the other side an untreated control and then underwent facelift procedure. Clinical evaluation by photographs was done prior to the surgical procedure. Ex vivo fragments were harvested from both sides and compared. Morphometric analysis of dermal collagen fibers, collagen synthesis, and elastin synthesis evaluations were compared in triplicates. RESULTS: Facial skin tightening was apparent in split-face photographs. A significant increase of 7.9% in dermal collagen content, and a significant increase of 34.7% in collagen synthesis were demonstrated in the treated samples. No statistically significant effect on elastin synthesis was detected. CONCLUSIONS: Skin tightening following treatment with non-invasive RF has proven histologically and biochemically to derive from increase in dermal collagen synthesis and content.

Who are the Pioneers? A Critical Analysis of Innovation and Expertise in Cutaneous Noninvasive and Minimally Invasive Cosmetic and Surgical Procedures.

BACKGROUND: Few studies illustrate the contributions made by various specialties in pioneering commonly performed noninvasive and minimally invasive cosmetic and surgical procedures. OBJECTIVE: To evaluate the contributions made by various specialties in pioneering noninvasive and minimally invasive cosmetic and surgical procedures. MATERIALS AND METHODS: Key words using the Medical Search Headings Database were used to query in the Thomson Reuters Web of Science Database. The 25 most highly cited studies were sorted according to the citation number. The author specialty was identified and assigned scores based on the number of citations. RESULTS: Dermatology was identified as the specialty with the greatest contribution to botulinum toxin treatments for rhytides, injectable fillers, laser treatments, chemical peels, and noninvasive body contouring. Neurology was identified as the leading specialty in botulinum toxin treatments for hyperhidrosis, and vascular surgery was identified as leading specialty in sclerotherapy. Plastic surgery was identified as having made the greatest contribution to hair transplantation, and liposuction. CONCLUSION: Dermatology was identified as the leading specialty for the majority of noninvasive and minimally invasive cosmetic procedures. Other specialties have also contributed important literature to this area.

A novel non-invasive radiofrequency dermal heating device for skin tightening of the face and neck.

BACKGROUND: Loose, lax skin is a common cosmetic complaint. Previous non-invasive skin tightening devices had modest efficacy and were associated with pain or downtime. New technologies may allow for effective skin tightening with a series of radiofrequency (RF) treatments with no downtime. OBJECTIVE: To evaluate the efficacy and safety of a novel bipolar RF device for skin tightening. METHODS: Fifteen consecutive female patients were enrolled in the case series; 14 completed the study and were included in the analysis. The device under investigation is a novel, bipolar RF device allowing for achievement and maintenance of optimal dermal temperatures to stimulate collagen remodeling and skin tightening. Patients underwent a series of 4-6 weekly treatments. Three blinded, experienced cosmetic physicians evaluated paired pre-treatment and post-treatment photographs and determined the associated improvement, if any. RESULTS: All patients (14/14) were determined to have a clinical improvement, as the pre-treatment and post-treatment photographs were correctly identified by the evaluators. It was observed that 21% (3/14) of patients had significant improvement, 50% (7/14) had moderate improvement, and 29% (4/14) had mild improvement. No pain, side effects, or adverse events were observed. CONCLUSIONS: This novel bipolar RF device represents a safe, effective treatment option for non-invasive skin tightening.

A clinical and biological evaluation of a novel, noninvasive radiofrequency device for the long-term reduction of adipose tissue.

BACKGROUND AND OBJECTIVE: A novel, noninvasive technology, utilizing suction-coupled radiofrequency (RF) heating and ultra-short pulse duration, high-voltage electrical pulses was studied for its efficacy and safety on adipose tissue reduction. METHODS: Twenty-one subjects underwent treatment of their abdominal fat once weekly for 6 weeks. Clinical outcomes including abdominal circumference, adipose tissue thickness (measured by ultrasound), adipose tissue weight, body weight, and clinical photographs were obtained at visits 1 and 3 months after last treatment. Adverse events were recorded. Three subjects, who were undergoing a future elective abdominoplasty, were treated with the same protocol, but on only one side of the abdomen before abdominoplasty. Biopsies from the RF-treated and untreated sides were harvested during abdominoplasty and cultured; measurements of adipocyte size and shape, rate of apoptosis, collagen production, and dermal thickness were determined. RESULTS: Significant clinical improvements (P < 0.05) were observed for the following clinical outcomes: reduction of abdominal circumference (113.4-110.7 cm), reduction of subcutaneous adipose tissue thickness (40.5-38.5 mm), and reduction in adipose tissue weight (32.2-30.7 kg) at 3-month follow-up visits. Overall patient weight also decreased, which was statistically significant at 1-month follow-up, but was not statistically significant at 3-month follow-up (73.9-73.3 kg, P = 0.609). Histologically, adipocytes were observed to have decreased size and withered shape, with increased levels of apoptosis; increased collagen synthesis, with compaction and reorganization of the dermis was also observed. Only minor, transient side effects were reported. CONCLUSIONS: This novel, noninvasive RF device was effective for improving subcutaneous fat, reducing abdominal circumference and reducing subcutaneous fat layer thickness. Histologically, these improvements appear to be partly related to increased adipocyte apoptosis.

Principles and practice of cutaneous laser and light therapy.

Laser technology has evolved rapidly in the last 2 decades. The theory of selective photothermolysis guides the proper selection and use of lasers to safely and effectively treat patients. This review summarizes the basic concepts and adjustable parameters for laser devices, emphasizing the importance of selective photothermolysis in clinical practice. It then covers the clinical applications of laser devices, including vascular lesions, hair removal, tattoo removal, facial rejuvenation, and fractional resurfacing. The authors intend to make the reader feel comfortable with the proper selection and application of lasers to treat their patients.

Modified Tripier flap for lateral eyelid reconstructions.

Eyelid defects can present many reconstructive challenges to surgeons; it is essential to maintain the function of the eyelid while avoiding tension vectors on the free margin, which could result in eyelid retraction. Thus, local skin flaps are often the closure option of choice for defects of the lateral eyelid. The Tripier flap was the first innervated myocutaneous flap to be reported, and was used for lateral lower eyelid repairs. The Tripier flap is a transposition flap utilizing redundant tissue on the upper eyelid to repair defects of the lateral inferior eyelid. The authors describe Their technique for the single-pedicle Tripier flap, which does not rely on the inclusion of orbicularis muscle or innervation. This modified Triper flap is a valuable addition to the reconstructive armamentarium of the dermatologic surgeon.

Cryolipolysis for reduction of excess adipose tissue.

Controlled cold exposure has long been reported to be a cause of panniculitis in cases such as popsicle panniculitis. Cryolipolysis is a new technology that uses cold exposure, or energy extraction, to result in localized panniculitis and modulation of fat. Presently, the Zeltiq cryolipolysis device is FDA cleared for skin cooling, as well as various other indications, but not for lipolysis. There is, however, a pending premarket notification for noninvasive fat layer reduction. Initial animal and human studies have demonstrated significant reductions in the superficial fat layer thickness, ranging from 20% to 80%, following a single cryolipolysis treatment. The decrease in fat thickness occurs gradually over the first 3 months following treatment, and is most pronounced in patients with limited, discrete fat bulges. Erythema of the skin, bruising, and temporary numbness at the treatment site are commonly observed following treatment with the device, though these effects largely resolve in approximately 1 week. To date, there have been no reports of scarring, ulceration, or alterations in blood lipid or liver function profiles. Cryolipolysis is a new, noninvasive treatment option that may be of benefit in the treatment of excess adipose tissue.

Melanoma and genetics.

As the incidence of malignant melanoma continues to increase and with the completion of the sequencing of the human genome, there have been increasing efforts to identify the "melanoma gene(s)." Although some patients and families have significantly increased risks due to genetic predisposition, most melanoma cases are sporadic and likely result from low to moderate risk genetic factors. This review focuses on the genes that cover the greatest risk of developing melanoma. It is important to remember that many--if not most--cases of melanoma are the result of undiscovered variants. The strongest genetic risk for the development of melanoma results from heritable alterations in cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, which encodes two separate but related proteins, p16/INK4a and p14/ARF. These proteins help regulate cell division and apoptosis, both of which are necessary to maintain cellular homeostasis. Other important genes include CDK4/6 and retinoblastoma (RB1), which encode downstream proteins in the same pathway as p16/INK4a and p14/ARF. Finally, we discuss the relative importance of the melanocortin 1 receptor (MC1R) gene as a moderate risk factor for melanoma. Although great advances have been made in understanding the molecular basis and genetic predisposition of melanoma, many questions still remain to be answered. Someday soon, it will be possible to predict a patient's risk of melanoma by DNA analysis; however, it is important to reconcile our tremendous technologic capabilities with documented clinical utility.

Isolated plantar collagenoma not associated with Proteus syndrome.

Isolated plantar cerebriform collagenomas are a relatively rare type of connective tissue nevus. They have been suggested to be pathognomonic of Proteus syndrome. However, their presence is now considered to be a major criterion of Proteus syndrome, but the diagnosis of Proteus syndrome also requires the presence of other minor criteria. We present an unusual case of an acquired plantar cerebriform collagenoma, which is not associated with Proteus syndrome. Collagenomas, or connective tissue nevi of the collagen type, represent a hamartomatous overgrowth of normal collagen. Isolated plantar collagenoma is rare, and most commonly presents in childhood. We report an interesting case of an isolated plantar cerebriform collagenoma in an adult.

Cost-effectiveness of biologic treatments for psoriasis based on subjective and objective efficacy measures assessed over a 12-week treatment period.

BACKGROUND: The cost-effectiveness of biologic agents is not well delineated. OBJECTIVE: To determine the cost-effectiveness of biologic agents in cost per patient achieving a minimally important difference in Dermatology Life Quality Index (DLQI MID) and cost per patient achieving a 75% improvement in Psoriasis Area Severity Index (PASI-75), assessed over a 12-week period. METHOD: Efficacies of the agents were determined through a literature review; treatment paradigms and associated costs were determined. The cost-effectiveness of the agents was determined and sensitivity analysis performed. RESULTS: Etanercept at a dose of 25 mg administered subcutaneously (SQ) once weekly was the most cost-effective agent in cost per patient achieving DLQI minimally important difference; infliximab at a dose of 3 mg/kg administered intravenously (IV) for 3 infusions, adalimumab at a dose of 40 mg SQ every other week, and etanercept at a dose of 25 mg SQ twice weekly were the next most cost-effective agents in cost per patient achieving the DLQI minimally important difference. Intravenous infliximab at a dose of 3 mg/kg was the most cost-effective agent in terms of cost per patient achieving PASI-75 improvement; intravenous infliximab at a dose of 5 mg/kg and adalimumab at a dose of 40 mg SQ every other week were the next most cost-effective agents in cost per patient achieving PASI-75 improvement. LIMITATIONS: This study had a limited time horizon of 12 weeks; generalizing the results to longer treatment periods may not be accurate and is not advisable. Additionally, when sensitivity analyses were performed, multiple agents had overlapping cost-effectiveness ratios at relatively low levels of variance; thus it may not be accurate to differentiate the cost-effectiveness of these agents. CONCLUSIONS: Different biologic agents for psoriasis appear to have different cost-effectiveness values; within the limitations of the available data, infliximab and adalimumab appear to be the most cost-effective agents.

How much of a topical agent should be prescribed for children of different sizes?

BACKGROUND: Compared with guidelines for the quantity of topical corticosteroids to apply in adults, standards for the use of topical corticosteroids in children are not well described. OBJECTIVE: To devise simple-to-use guidelines for topical corticosteroid quantities needed in infants, children, pre-teens, and adults. METHODS: We determined body surface area (BSA) using mean heights and weights in order to calculate the appropriate quantities of medication to be prescribed. RESULTS: As a rough estimate, infants require one-fifth of adult doses, children two-fifths of adult doses, and adolescents two-thirds of adult doses. However, the assessment of BSA may vary considerably between clinicians. Patients may also vary in how thickly they apply topical medication. CONCLUSIONS: A simple guideline for how much topical corticosteroid to prescribe may facilitate the treatment of young children with skin disease.

New treatments for psoriasis: which biologic is best?

Psoriasis is a chronic, debilitating disease affecting not only the skin, but also having a significant impact on a patient's quality of life. The treatment of severe psoriasis is quite challenging due to the chronic, relapsing nature of the disease and the difficulties inherent in treatment planning. Though the biologics are perhaps the most promising of available psoriasis treatments, the decision to institute a given therapy may be fraught with complexity for the clinician. Patients now hear of these promising new treatments for psoriasis via print, television and radio advertising; they frequently come to their physician asking if they are eligible for any of these agents and, if so, 'which biologic is best?'. This paper attempts to determine the ideal biologic agent based upon several parameters: FDA- and EU-approved indications, therapeutic efficacy, impact on quality of life, cost-effectiveness, and safety profile. Certainly the physician is central to medical decision-making, though ultimately patient preference may play the largest role in determining the 'best' biologic agent. There is no single ideal biologic for all patients and a physician's job is to educate patients on the relative advantages and disadvantages of each agent. Through informed discussion, the clinician can help each individual patient decide which biologic agent is ideal for them.

The cost-effectiveness and cost of treatment failures associated with systemic psoriasis therapies.

BACKGROUND: Psoriasis is difficult at times to treat and treatment failures are not uncommon regardless of approach. With the advent of expensive biologic therapies for psoriasis there is increasing discussion on the cost efficacy of a given systemic or biologic agent. An alternative and overlooked aspect of cost efficacy is the cost that accrues from treatment failures. METHODS: We review the literature and develop a model to analyze the cost-effectiveness and the cost of treatment failures per success for various systemic psoriasis agents using a 12-week treatment period. RESULTS: For continuous-dose agents, the cost-effectiveness results are: methotrexate $623, acitretin $2729, cyclosporine $2969, nUVB $3692, PUVA $4668, etanercept $16 312, and efalizumab $17 196. The cost of expected treatment failures to achieve one success for the same agents were: methotrexate $187, cyclosporine $505, PUVA $767, nUVB $1034, acitretin $1310, etanercept $8319, and efalizumab $12 897. CONCLUSIONS: Methotrexate appears to be the most cost-effective agent for the treatment of severe psoriasis. However, greater efficacy can be achieved with cyclosporine and PUVA, albeit at a greater cost. Because of the high cost of treatment failures, access to a wide array of therapies and combination regimens should not be discouraged by physicians or insurers.

Cost analysis of functional restoration surgery for extremity soft-tissue sarcoma.

BACKGROUND: Limb-sparing surgery, consisting of wide-margin tumor resection and preoperative or postoperative radiotherapy/chemotherapy, has become the surgical treatment of choice for extremity sarcomas. However, adequate tumor resection can sometimes compromise crucial limb function, necessitating functional restoration surgery. The purpose of this study was to determine the cost impact and functional outcomes of such procedures. METHODS: Patients receiving either functional restoration surgery or soft-tissue-only reconstruction following extremity soft-tissue sarcoma excision were identified. Patients were then compared along several dimensions: overall length of stay and its subdivisions, surgical time, and total charges and its subdivisions. Patients' functional outcomes were assessed with the Toronto Extremity Salvage Score. RESULTS: Sixty-seven patients who underwent 69 limb-sparing procedures were identified. Fifteen of these procedures (eight upper extremity, seven lower extremity) required functional restoration surgery; 54 of these procedures (13 upper extremity, 41 lower extremity) required only soft-tissue coverage. In the upper extremity, there was a statistically significant increase in overall length of stay (2.8 days) and its subdivisions, surgical time (3.7 hours), and total charges (12,484 dollars) and its subdivisions associated with performing functional restoration surgery. In lower extremity cases, statistically significant increases were determined in only the total charges (9190 dollars) and medical supply charges (13,204 dollars) following functional restoration. Patients who underwent functional restoration surgery had better postoperative function (mean Toronto Extremity Salvage Score, 82 versus 80), but this difference was not statistically significant. CONCLUSION: Although functional restoration surgery is more costly than soft-tissue reconstruction alone, the authors believe that the associated better functional outcome justifies its performance.

Inpatient management of severe psoriasis.

Historically, severe psoriasis frequently required inpatient hospitalization for several weeks to reduce symptoms and prevent morbidity and mortality, Despite declining hospitalization rates there remain patients who undergo severe, acute psoriasis exacerbations requiring inpatient care. The majority of the literature describes the treatment of psoriasis in the outpatient setting. We review the inherent differences between the inpatient and outpatient management of psoriasis along several dimensions and discuss an approach to the inpatient treatment of severe psoriasis based upon therapeutic rate of onset, efficacy, and safety. The inpatient setting benefits from and lends itself to use of rapid acting, highly effective agents. Given the acute nature of psoriasis inpatient episodes, the risks associated with long-term use of a treatment are far less important in inpatient setting treatment planning than they are in the outpatient setting.

Infliximab for inpatient psoriasis management--is there a role?

BACKGROUND: While outpatient management is a realistic goal for most psoriasis patients, inpatient hospitalization may be required for severe acute exacerbations. The paradigm of inpatient psoriasis treatment has changed as reflected in an overall decline in admissions as well as the introduction of several new agents for patients with moderate to severe disease. With these changes as well as the changes in inpatient health care delivery, the costs of inpatient psoriasis therapy need to be re-examined. PURPOSE: To determine the mean charges and length of stay associated with inpatient admissions for psoriasis and compare these with the potential charges for infliximab administration in the inpatient setting. METHODS: Inpatient psoriasis admissions were identified from the State of Maryland Health Services Cost Review Commission (HSCRC) non-confidential database from 1994 to 2003. The mean length of stay and total charges associated with psoriasis admissions were determined and adjusted to current values based upon the hospital costs component of the Consumer Price Index (CPI). The potential charges for infliximab administration were then estimated according to a presumed treatment paradigm and based on median Medicare reimbursement rates. RESULTS: The mean length of stay for an inpatient psoriasis patient was 4.9 days, and the mean CPI adjusted total charges from 1994 to 2003 were $6736. In 2003, the mean total charges for a psoriasis admission were $7578. The total estimated charges for a 2-day inpatient hospitalization with infliximab administration were $6256. CONCLUSIONS: Although infliximab therapy is not currently approved for psoriasis therapy it does have efficacy and may be a first-line therapy for inpatient treatment. Additionally, the high cost of infliximab may be offset by a decreased overall length of stay and its use is therefore potentially justified.