Dermatology
03 Jun Sun Sensitive, Skin Cancer Prone Patients Responsive To Prevention Messages
MedicalResearch.com Interview with:
Catherine M. Olsen, PhD
Population Health Department
QIMR Berghofer Medical Research Institute
Queensland, Australia
MedicalResearch: What is the background for this study?
Dr. Olsen: Effective skin cancer control requires two strategies: regular sun protection to prevent new cancers from occurring and early detection assisted by periodic skin examinations. The aim of our study was to describe the prevalence and predictive factors for sun protection and skin examination practices of adults in Queensland, Australia, a region that experiences the highest rates of skin cancer in the world. We were particularly interested in whether sun protection and skin examination practices differed between those with and without a previously confirmed melanoma and/or treatment for other skin lesions.
MedicalResearch: What are the main findings?
Dr. Olsen: The prevalence of both sun protection and skin examination practices was generally high in this large cohort of people who experience high levels of ambient sun exposure.
People who had been diagnosed with a melanoma or other skin lesion were more likely than those without to report sun protection practices including regular use of sunscreen and wearing hats.
The strongest predictor of sun protection practices was having a sun-sensitive skin type, and the strongest predictor of skin examination practices was having many moles and/or a family history of melanoma.
29 May Long Term Adverse Reactions To Tattoos Surprisingly Common
MedicalResearch.com Interview with:
Dr. Marie C. Leger, MD, PhD
Assistant Professor
Ronald O. Perelman Department of Dermatology
NYU Langone Medical Center
Medical Research: What inspired this study? How did it come about?
Dr. Leger: As a dermatologist at NYU, I have taken care of several patients with tattoo reactions--some of them mild (like longstanding itching for example) and some of them more severe (like long term reactions to a particular color that can severely disfigure the tattoo) and wondered how common it was for people to have adverse tattoo reactions or complications. There were lots of case reports in the literature but only a few larger studies examining how common these kinds of complaints were--and these were all European studies. We decided to do a quick survey to give us a better idea of how common it is for people to have problems with their tattoos.
Medical Research: What do you think is the most important takeaway from this study for the consumer?
Dr. Leger: Tattoos have risks associated with them--which is part of their appeal I'm sure--but I do think it's important for people to know that long term tattoo reactions (including for example, itching, scaling, swelling) may be more common than we realize. A recent Danish study shows that these kinds of reactions can be quite distressing for people and significantly impact their quality of life.
26 May Not All Biologics For Psoriasis Carry Same Risk Of Serious Infections
MedicalResearch.com Interview with:
Robert E Kalb, M.D.
Clinical Professor of Dermatology
State University of New York at Buffalo School of Medicine and Biomedical Sciences
Buffalo Medical Group, P.C.
Buffalo, NY 14221
Medical Research: What is the background for this study? What are the main findings?
Dr. Kalb: It's important to evaluate the safety of biologics in the real world post-marketing setting, and in particular with respect to serious infections. We studied patients with psoriasis in the PSOLAR registry and evaluated the risk of various biologic therapies. We found that infliximab and adalimumab were associated with increased risk of serious infections when compared with non-biologic/non-methotrexate therapies, while ustekinumab and etanercept were not associated with increased risk.
18 May Rosacea: Metronidazole Plus Modified Release 40 Mg Doxycycline Improved Moderate To Severe Disease
MedicalResearch.com Interview with:
Warren J. Winkelman, MD, MBA, PhD, FRCPC, FAAD
Director, Medical Affairs
Galderma Laboratories, L.P.
Fort Worth TX 76177
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Winkelman: Rosacea is a common dermatologic facial disorder estimated to affect 16 million Americans. Rosacea is a chronic condition of the central face, including the nose, chin, cheeks and forehead, and is often characterized by flare-ups and remissions. While the cause of rosacea is unknown and there is no cure, its signs and symptoms can become markedly worse in the absence of treatment. Rosacea can be managed with topical and oral medications, and physicians often resort to using these medications in combination for more severe or resistant cases. Doxycycline 40 mg modified release (MR) and metronidazole 1% gel are FDA-approved oral and topical therapies, respectively, indicated to treat the papules and pustules of rosacea. We conducted a phase 2 study to assess the relapse rate, efficacy, and safety of doxycycline 40 mg MR compared to placebo after an initial 12-week once-daily combination regimen of doxycycline 40 mg MR and metronidazole 1% gel in subjects with moderate to severe disease.
Of the 235 subjects enrolled in the study, 71% were women, 94% were white, and 75% had Fitzpatrick skin type I, II or III. The mean age was 47.4 years. The percentage of subjects who achieved a success score of 0 (clear) or 1 (near clear) improved from 0% at baseline to 51% at week 12. Clinician’s erythema assessment scores, inflammatory lesion counts, and quality of life scores also improved. Most subjects reported no or mild scaling, stinging/burning, and dryness. Five adverse events were reported that were considered probably or definitely related to treatment: fungal infection, vulvovaginal mycotic infection, pain in extremity, erythema, and skin exfoliation.
02 May Rosacea Improved With Modified Release Doxycycline 40 mg Plus Topical Metronidazole
MedicalResearch.com Interview with:
Warren J. Winkelman, MD, MBA, PhD, FRCPC, FAAD
Director, Medical Affairs
Galderma Laboratories, L.P.
Fort Worth TX
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Winkelman: Rosacea is a common dermatologic facial disorder estimated to affect 16 million Americans. Rosacea is a chronic condition of the central face, including the nose, chin, cheeks and forehead, and is often characterized by flare-ups and remissions. While the cause of rosacea is unknown and there is no cure, its signs and symptoms can become markedly worse in the absence of treatment. Rosacea can be managed with topical and oral medications, and physicians often resort to using these medications in combination for more severe or resistant cases. Doxycycline 40 mg modified release (MR) and metronidazole 1% gel are FDA-approved oral and topical therapies, respectively, indicated to treat the papules and pustules of rosacea. We conducted a phase 2 study to assess the relapse rate, efficacy, and safety of doxycycline 40 mg MR compared to placebo after an initial 12-week once-daily combination regimen of doxycycline 40 mg MR and metronidazole 1% gel in subjects with moderate to severe disease.
Of the 235 subjects enrolled in the study, 71% were women, 94% were white, and 75% had Fitzpatrick skin type I, II or III. The mean age was 47.4 years. The percentage of subjects who achieved a success score of 0 (clear) or 1 (near clear) improved from 0% at baseline to 51% at week 12. Clinician’s erythema assessment scores, inflammatory lesion counts, and quality of life scores also improved. Most subjects reported no or mild scaling, stinging/burning, and dryness. Five adverse events were reported that were considered probably or definitely related to treatment: fungal infection, vulvovaginal mycotic infection, pain in extremity, erythema, and skin exfoliation.
23 Apr Gene Expression Profile Improves Melanoma Risk Assessment
MedicalResearch.com Interview with:
Pedram Gerami, M.D.
Associate Professor of Dermatology
Director, Melanoma Research
Northwestern Skin Cancer Institute
Northwestern University
MedicalResearch: What is the basis and background for performing this study?
Dr. Gerami: Most of the existing literature shows that Sentinel Lymph Node Biopsy (SLNB) will identify 25 to 35 percent of patients who will ultimately die of metastatic melanoma. Hence while SLNB is reported to be the strongest predictor of outcome for melanoma, the vast majority of patients who ultimately die of metastatic melanoma have a negative Sentinel Lymph Node Biopsy result. Hence in this study we aimed to determine whether a GEP assay developed by Castle bioscience could be used independently or in conjunction with SLNB to better detect those patients who are at high risk for developing metastatic disease and dying from melanoma.
MedicalResearch: What are the findings of the study?
Dr. Gerami: Our study, which examined the use of a Gene Expression Profile (GEP) assay developed by Castle Biosciences and Sentinel Lymph Node Biopsy alone and in combination in a multi-center cohort of 217 patients, demonstrated that the use of the GEP identified more than 80 percent of patients who develop melanoma
Combining the two methods showed that patients predicted to be high risk based on the GEP test alone had similar rates of disease progression whether they were SLNB positive or negative. Patients who were SLNB negative and predicted to be low risk using the GEP test had lower rates of disease progression than the SLNB negative group as a whole.
11 Apr Herpes Zoster Risk May Be Elevated In Psoriasis Patients On Combination Therapy
MedicalResearch.com Interview with: Arnon D. Cohen, MD, MPH, PhD Department of Quality Measurements and Research, Chief Physician's Office, Clalit Health Services, Tel Aviv Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel MedicalResearch: What is the background for this study? Dr. Cohen: Herpes zoster (HZ),...
08 Apr New Antiviral Medication For HPV Infection Shows Promise
MedicalResearch.com Interview with: Luis Squiquera, MD Tamir Biotechnology MedicalResearch: What is the background for this study? What are the main findings? Dr. Squiquera: Ranpirnase is a small peptide that has a characteristic enzymatic activity against double stranded RNA (dsRNA). As a drug it has been extensively tested intravenously in high concentration for oncology in over 1000 patients with different types of malignancy, especially mesothelioma, with minimal side effects and mainly a transient increase of serum creatinine level observed. In the last year we started a comprehensive antiviral program and obtained encouraging results in several RNA and DNA virus families. Several research groups have already studied the anti HIV activity. HPV was one of many viruses that showed a high selectivity index in our antiviral screening (the relationship between efficacy and cytotoxicity). We were encouraged by the low concentrations (nanomolar range) needed to stop virus reproduction in cell cultures. We performed in vitro analysis of two of the main HPV types that cause human disease (HPV 11 and 16). HPV 11 was highly sensitive to ranpirnase; and since this is one of the main virus type responsible for inducing genital warts, we decided to focus our efforts in bringing the drug to a new route of administration. We set out to obtain and did obtain a formulation that was extremely stable, even at high temperatures. Before using it in patients, we performed testing for irritation using standardized Draize animal models. Even though we ran these tests in high concentrations (1 mg/ml) the final product was not irritant and was deemed safe to use in a clinical setting. With these safety data on hand – plus extensive experience in IV dosing and non-irritation in animal models – we decided to make the formulation available as a compassionate use for patients with genital warts. As we reported in our presentation in San Francisco, all cases that completed an 8-week treatment showed clearance of the lesions. Some of the cases were cleared in as soon as two weeks and the average time for clearance was 33 days. One of the patients had to be discontinued due to an eczematous skin reaction. We will be studying the characteristic of this effect in our trials.03 Apr No Matter How It’s Applied, Eyeliner Often Gets Into The Eyes
Alison Ng PhD, BSc(Hons), MCOptom
Post-Doctoral Fellow
Centre for Contact Lens Research
School of Optometry & Vision Science
University of Waterloo
Waterloo, Ontario Canada
Medical Research: What is the background for this study? What are the main findings?
Dr. Ng: Eye care practitioners often see patients coming into our clinics with eyeliner “floating” in the tears or adhered to the surface of contact lenses during our routine examinations. When products such as eyeliner enters and contaminates the tear film, some patients complain of temporary discomfort, and if they wear contact lenses, they may report blurred vision if the lenses become spoiled. Specifically in this pilot study, we wanted to look at how differently eyeliner migrated into the tear film when applied in two different ways: inside the lash line and outside of the lash line.
03 Apr Sunsmart Mass Media Campaign Encourages Sun Protection
MedicalResearch.com Interview with:
Suzanne Dobbinson PhD
Senior Research Fellow
Centre for Behavioural Research in Cancer
Cancer Council Victoria Melbourne Australia
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Dobbinson: Australia has one of the highest skin cancer rates in the world due to the country’s high levels of ultraviolet (UV) radiation and a population with susceptible skin types. Two in three Australians will be diagnosed with skin cancer by the age of 70, with more than 40,000 new cases annually in the state of Victoria alone.
Since the 1980s there have been broad public education programs to raise awareness of skin cancer. Television campaigns have been central to these multi-component prevention programs, including SunSmart, which is the longest-running program in Victoria.
This study examined SunSmart television advertisements broadcast over summers between 1987 to 2011 to determine what effect – if any – these advertisements had on people’s sun protection attitudes and behaviours.
Cross-sectional weekly telephone surveys of Melbourne residents were conducted over summers during the study period. Population exposure to campaign TV advertisements was also measured as cumulated weekly target audience rating points (TARPs) for 4 weeks prior to interview. Using multiple logistic and linear regression models, we examined whether there was a relationship between the TARPs and responses of the surveys.
We found that increasing TARPs were related to an increased preference for no tan, increased sunscreen use and overall reduced mean percentage of skin exposed to the sun. Also of note was that this behavioural impact was consistent across all age groups.
03 Apr RNA Sequencing Helps Unravel Disease Pathology In Atopic Dermatitis
MedicalResearch.com Interview with:
Emma Guttman-Yassky, MD, PhD
Department of Dermatology
Icahn School of Medicine at Mount Sinai Medical Center
New York, NY 10029
Medical Research: What is the background for this study? What are the main findings?
Dr. Guttman-Yassky: Atopic dermatitis/AD is the most common inflammatory skin disease. Increased knowledge about the molecular phenotype of atopic dermatitis has contributed to development of novel therapeutics, including trials with targeted therapeutics. Genomic skin data from these trials largely rely on microarrays that are based on hybridization of labeled RNA/cDNA to single stranded DNA sequences that translate to expression levels. We have recently shown that the atopic dermatitis transcriptome (defined as differentially expressed genes [DEGs] between lesional and non-lesional skin) is reversible with broad and specific therapeutics. For future mechanistic studies within clinical trials, it is important to determine the agreement between microarrays and RNA-seq and to evaluate whether RNA-seq offers additional benefits. This is the first report of the lesional atopic dermatitis phenotype by RNA-seq, and the first direct comparison between the microarray and RNA-seq platforms in this disease. Both platforms robustly characterize the AD transcriptome. Through RNA-seq, we unraveled novel atopic dermatitis disease pathology, including increased expression of the novel TREM-1 signaling pathway and IL-36 cytokine, which might have a pathogenic role in atopic dermatitis. Importantly, good agreement with real time PCR, which serves as the "gold standard" for detection of gene expression was observed for both technique. Overall good agreement was observed with RT-PCR for both RNA-seq and microarrays, but key atopic dermatitis immune cytokines (such as interleukin 13, and interleukin 22), which are highly elevated in atopic dermatitis lesions were only detected by RT-PCR. Overall, both RNA-seq and microarrays can similarly characterize the lesional AD transcriptome and serve as valuable tools for molecular tissue studies within large clinical trials and a core atopic dermatitis pathology is common to microarray and the RNA-seq transcriptomes. RNAseq might play a complementary role for unravelling novel disease pathology, although analyses tools for RNAseq are still being developed.
03 Apr Genital Psoriasis Negatively Impacts Quality of Life and Sexual Function
Posted at 00:57h
in Author Interviews, Baylor University Medical Center Dallas, Dermatology, Sexual Health
MedicalResearch.com Interview with:
Caitriona Ryan, MD
Baylor University Medical Center, Dallas
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Ryan: Psoriasis is a common, chronic, inflammatory disorder of the skin which has a considerable impact on social functioning and personal relationships. Genital involvement can have devastating psychosexual implications for psoriasis patients. In a study examining the stigmatization experience in psoriasis patients, involvement of the genitalia was found to be the most relevant, regardless of the overall psoriasis severity. Although sexual function is an integral component of quality of life, dermatology-specific and psoriasis-specific scales largely neglect the impact of disease on sexual health. Despite major advances in other aspects of psoriasis research, there has been little emphasis in recent times on the identification and treatment of genital psoriasis and few studies have examined predisposing risk factors, phenotypical associations or its impact on quality of life and sexual functioning.
This study was designed to examine the prevalence and nature of genital involvement in patients with psoriasis, to ascertain risk factors for the development of genital psoriasis, to determine the impact of genital disease on quality of life and sexual functioning, and to assess patient satisfaction with current topical treatments for genital psoriasis.
28 Mar Psoriasis: Effective Two Year Response to IL-17A Antagonist Cosentyx
MedicalResearch.com Interview with:
Andrew Blauvelt, M.D., M.B.A.
President and Investigator
Research Excellence & Personalized Patient Care
Portland, OR 97223
Medical Research: What is the background for this study? What are the main findings?
Dr. Blauvelt: A2303E1 is a multicenter, double-blind, randomized withdrawal extension to the FIXTURE and ERASURE pivotal phase III studies. The purpose of this extension study was to collect additional long term efficacy, safety, and tolerability data on secukinumab (i.e., Cosentyx) in patients who demonstrated a PASI 75 response to Cosentyx at Week 52 of these core studies in moderate-to-severe plaque psoriasis.
In the extension phase, 995 patients who achieved Psoriasis Area Severity Index (PASI) 75 responses after 52 weeks of therapy received either Cosentyx 300 mg, Cosentyx 150 mg, or placebo for an additional year (Week 104). After two full years of therapy in patients treated with Cosentyx 300 mg, almost 9 out of 10 (88.2%) patients maintained their PASI 75 response, 7 out of 10 (70.6%) had clear or almost clear skin (PASI 90), and 4 out of 10 (43.9) had clear skin (PASI 100) at Week 104. For patients treated with Cosentyx 150 mg, 75.5% maintained their PASI 75 response, 44.6% had clear or almost clear skin (PASI 90), and 23.5% had clear skin (PASI 100) at Week 104. In addition, 94.8% of patients who initially received placebo (at the start of the extension), and were switched to receive Cosentyx 300 mg after relapse, were able to achieve PASI 75 and 70.3% achieved PASI 90 within 12 weeks of re-starting Cosentyx.
27 Mar Senna May Relieve Itching In Some Dialysis Patients
Posted at 01:35h
in Author Interviews, Baylor University Medical Center Dallas, Dermatology, Kidney Disease
MedicalResearch.com Interview with:
Mohammad Kazem Fallahzadeh Abarghouei, M.D.
Baylor University Medical Center, Dallas, TX
Medical Research: What is the background for this study?
Response: Uremic pruritus (itch) is a common problem in hemodialysis patients. No effective treatment exists for uremic pruritus due to its complex pathogenesis. Systemic inflammation and elevated serum levels of interleukin-2 (IL-2) are implicated in the pathogenesis of uremic pruritus. Senna is an herbal drug commonly used for treatment of constipation. Senna also has anti-inflammatory properties. We performed this randomized double-blind placebo-controlled trial to evaluate the effect of senna on reduction of uremic pruritus and serum levels of IL-2 in hemodialysis patients.
26 Mar Imiquimod Cream May Be Effective In Primary And Adjuvant Treatment Of Lentigo Maligna
MedicalResearch.com Interview with:
Susan Swetter, MD
Professor of Dermatology and Director, Pigmented Lesion and Melanoma Program
Stanford University Medical Center and Cancer Institute.
Medical Research: What is the background for this study?
Dr. Swetter: This retrospective cohort study sought to explore the role of the topical immunomodular - imiquimod 5% cream - as both primary and adjuvant therapy (following optimal surgery) for patients with the lentigo maligna subtype of melanoma in situ. Assessment of alternative treatments to surgery for this melanoma in situ subtype are warranted given the increasing incidence of lentigo maligna in older, fair-complexioned individuals in the United States. Surgical management of lentigo maligna is complicated by its location on cosmetically sensitive areas such as the face, histologic differentiation between lentigo maligna and actinic melanocytic hyperplasia in chronically sun-damaged skin, and potential surgical complications in the elderly who may have medical co-morbid conditions.
Medical Research: What are the main findings?
Dr. Swetter: We conducted a retrospective review of 63 cases of lentigo maligna in 61 patients (mean age 71.1 years) who used topical 5% imiquimod cream instead of surgery (22 of 63 cases, 34.9%) or as an adjuvant therapy following attempted complete excision (63 cases, 65.1%), in which no clinical residual tumor was present but the histologic margins were transected or deemed narrowly excised. Our study showed overall clinical clearance of 86.2% in the 58 patients analyzed for local recurrence at a mean of 42.1 months of follow-up (standard deviation 27.4 months), with primarily treated cases demonstrating 72.7% clearance at a mean of 39.7 months (standard deviation 23.9 months), and adjuvant cases showing 94.4% clearance at a mean of 39.7 months (standard deviation 23.9 months). We found a statistically significant association between imiquimod-induced inflammation and clinical or histologic clearance in primary but not adjuvant cases, although this latter finding may be explained by a lack of residual atypical melanocytes or true LM in the adjuvant setting, in which wide local excision had already been performed.
24 Mar More Asians and Hispanics Developing Non-Melanoma Skin Cancer
MedicalResearch.com Interview with: Arisa Ortiz, MD, FAAD Assistant Clinical Professor Director, Laser and Cosmetic Dermatology Senior author: Brian Jiang, MD and First author Tiffany Loh, BS Department of Dermatology UC San Diego Medical Research: What is the background for this study? What are the main findings? Response: Non-melanoma skin cancers (NMSCs) are the most common type of malignancy in the United States, affecting an estimated 3.5 million people each year. Previous perception has remained that skin cancer risk in Hispanics and Asians is lower than that of Caucasians. However, despite historically lower rates of skin cancer, in recent years, the incidence of skin cancer in these groups has reportedly been increasing in the United States. As Hispanics and Asians constitute two of the most rapidly expanding ethnic groups in the US, the rise in NMSCs in these populations is particularly concerning. The finding from our study were as follows: Hispanic patients were significantly younger than Caucasians and Asians (p=0.003, 0.023 respectively). The majority of Non-melanoma skin cancers in Caucasians occurred in men, while this gender ratio was reversed for both Hispanics and Asians. There were significantly more cases of Non-melanoma skin cancers occurring in the “central face” area in Hispanics. Race was not a significant predictor for specific NMSC type (BCC or SCC).24 Mar Opioid Analgesics Prescribed In Patients With Skin Disorders and Psychiatric Diagnoses
MedicalResearch.com Interview with:
Madhulika A. Gupta MD
University of Western Ontario
Medical Research: What is the background for this study? What are the main findings?
Dr. Gupta: Opioid (narcotic) analgesics (OA) are FDA-approved primarily for the symptomatic relief of pain in acute and chronic conditions. The prescription rates of Opioid analgesics in the US have increased significantly since 1989, and their possible inappropriate use has been declared a public health concern. We have recently reported (GuptaMA et al. J Dermatol Treat, 2014) that the use of Opioid analgesics in primarily skin disorders (with no reported non-dermatologic comorbidities) has increased from 1995-2010. Skin disorders are associated with psychiatric pathology in up to 30% of cases. Psychiatric disorders have been associated with an increased use of Opioid analgesics and other potentially addictive drugs. We examined psychiatric disorders, comorbidities and psychotropic drugs in patient visits with skin disorders and Opioid analgesics use (‘Skin Disorders+OA’).
We examined nationally representative cross-sectional data collected between 1995-2010 by the NAMCS and NHAMCS. Up to 3 ICD9-CM diagnoses are coded for each patient visit; the following codes were used to create the ‘Skin Disorders’ variable: ICD9-CM codes 680-709 ‘Diseases of the Skin and Subcutaneous Tissue’ and ICD9-CM codes 172, 173, 216 and 232 for cutaneous malignancies. Ambulatory Care Drug Database System drug codes were used for creation of variables for Opioid analgesics and other psychotropics.
22 Mar Acne: Potassium Monitoring May Not Be Necessary For Spironolactone Therapy
MedicalResearch.com Interview with:
Dr. Arash Mostaghimi, MD, MPA
Director of Dermatology Inpatient Service
Brigham and Women’s Hospital
Boston, MA
Medical Research: What is the background for this study? What are the main findings?
Dr. Mostaghimi: Spironolactone, a generic drug that’s been used in the clinic since 1959, is commonly prescribed for treating hormonal acne – acne that tends to affect the jaw line most commonly around the time of the month when a woman gets her period. The US Food and Drug Administration recommends frequent potassium monitoring in patients with heart failure who are taking spironolactone as a diuretic and antihypertensive treatment, but it’s been unclear if these guidelines should apply to healthy patients taking spironolactone for the treatment of acne, and, if so, how frequently such patients should have their potassium levels tested.
My colleagues and I have found that for young, healthy women taking spironolactone to treat hormonal acne, potassium monitoring is an unnecessary health care expense. For the approximately 1,000 patients we studied, blood tests to monitor potassium levels did not change the course of treatment, but the tests cumulatively totaled up to $80,000. We suggest that routine potassium monitoring should no longer be recommended for this patient population in order to improve the patient care experience, decrease unnecessary office visits and reduce health care spending.
22 Mar Topical Spironolactone May Limit Skin Thinning From Steroids
MedicalResearch.com Interview with: Nicolette Farman MD Ph.D. Directeur de recherche Université Pierre et Marie Curie, Paris, France Centre de Recherche des Cordeliers Paris, France Medical Research: What is the background for this study? What are the main findings? Dr. Farman: I have been working for a long time on aldosterone, a steroid hormone that enhances renal sodium transport, thus regulating blood pressure levels. Importantly, excessive effects of the hormone can be blocked by a pharmacological agent (a blocker of the receptor of the hormone): spironolactone. This drug has been used for decades as an anti-hypertensive drug. We identified several tissues where the receptor for the hormone (the mineralocorticoid receptor, MR) is expressed, in addition to kidney cells. Unexpectedly we found the receptor to be present in the human epidermis, but its role there was ignored. We designed first a mouse model, and found that overexpression of the receptor leads to thin and fragile skin in mice, as observed in glucocorticoid-treated skin. We hypothetized that perhaps the glucocorticoids exhibit this deleterious side-effect because they could bind to the mineralocorticoid receptor. As a consequence, we argued that pharmacological blockade of the MR over the skin should limit this side-effect. We used human skin explants in culture, and treated them with a potent dermocorticoid (clobetasol) alone or together with spironolactone. After 5 days in culture, we saw that spironolactone could indeed limit the atrophy of the epidermis induced by the dermocorticoid. Then a clinical trial was performed in healthy volunteers, that confirmed the efficiency of topical spironolactone to limit glucocorticoid-induced atrophy. Although the effect is not full reversion, the benefit was there. This is why we propose now that this approach could bring benefit to patients, if our results are confirmed in patients with psoriasis or eczema, that receive a dermocorticoid cream or gel.22 Mar Apremilast -Otezla -May Be Cost Effective For Psoriasis Treatment
MedicalResearch.com Interview with: Steven R. Feldman, M.D., Ph.D. Professor of Dermatology Wake Forest Baptist Medical Center Winston-Salem, NC Medical Research: What is the background for this study? What are the main findings? Response: Results show that introducing apremilast into the treatment pathway prior to biologics is cost-saving and confers a cost and quality of life benefit. Over 10 years, apremilast was estimated to provide an additional 0.74 years (5.00 vs. 4.26 years) in which patients achieved a 75% reduction from baseline in PASI score, compared to a pathway of biologics only. It was also found to be less costly, mainly due to less time spent on more expensive biologic therapy (costs reduced by $9,072.39 over 10 years).15 Mar Bacterial DNA Detected In Blood Of Patients With Active Psoriasis
MedicalResearch.com Interview with:
Dr. Ana Ramírez-Boscá, MD
Department of Dermatology and Clinical Research Unit and
Vicente Navarro-López, MD
Clinical Research Unit and Infectious Diseases Unit
Centro Dermatológico Estético, Alicante, Spain
MedicalResearch: What is the background for this study? What are the main findings?
Response: Infections have been related with the pathogenesis of guttate psoriasis, however antibiotic treatment does not improve prognosis nor does it affect the evolution of the disease. The association between psoriasis and other infectious diseases has been reported as well, although in these cases there is scarce information on the causative microbial likely involved and the role of these bacteria in the pathogenesis of this skin disease.
MedicalResearch: What are the main findings?
Response: Bacterial DNA may be detected in bloodstream of a significant proportion of patients with active plaque psoriasis. Increased levels of pro-inflammatory cytokines in patients with presence of bacterial DNA but not in patients without presence of bacterial genomic fragments suggest a role of bacterial DNA translocation in inducing an inflammatory response.
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Guttate Psoriasisfrom Wikipedia[/caption]
11 Mar Chinese Licorice May Enhance Skin Protection From Sun Exposure
MedicalResearch.com interview with: J. Kühnl, D. Roggenkamp, G. Neufang. Research & Development, Beiersdorf AG, Hamburg MedicalResearch:What is the background for this study? What are the main findings? Response: The skin is constantly challenged by environmental stressors that induce inflammatory processes, resulting in skin damage and –in the long term- consequently aging processes. UV-irradiation is an important exogeneous stressor. Even the best filter systems do not completely abolish the impact of UV radiation. For example, after application of a SPF50+ sun lotion, about 2% of UV-rays still reach the skin. However, the skin developed strategies to cope with exogenous stressors: Intracellular thiols quench harmful UV-derived free radicals and a multitude of detoxifying enzymes convert noxious compounds and metabolites into harmless species. We strived to specifically stimulate these cytoprotective cellular systems in order to tip the balance in favor of more robust skin cells. Previous studies showed that the root extract of the plant Glycyrrhiza inflata (Chinese Licorice) exhibits anti-inflammatory and anti-microbial effects. The major phenolic constituent of the licorice extract is Licochalcone A (LicA) and this compound is largely responsible for the beneficial effects. This was explained by LicA´s inhibitory effect on the pro-inflammatory transcription factor NFkB and its antioxidant properties. However, in this study, we could add another facet of LicA´s efficacy: by activating the transcription factor Nrf2, LicA stimulates the expression of cytoprotective enzymes such as heme oxygenase I and the key enzyme of glutathione synthesis, resulting in increased intracellular thiols concentrations. Consequently, when pre-incubated with LicA, isolated human skin cells were more robust against solar simulated light-induced cellular damage, indicated by a significantly decrease in the generation of free radicals in vitro. In a translational approach, we conducted a study with healthy volunteers demonstrating that the application of a lotion containing LicA-rich root extract on the inner forearms for two weeks protected the skin from UV-provoked oxidative stress. Thus the cellular effects of licorice are able to provide a protective shield from sun exposure, supporting and going beyond the action of sunscreens regarding sun protection.06 Mar Genetic Study Confirms Most Pediatric Melanoma Linked To Sun Exposure
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Dr. Pappo and Dr. Bahrami[/caption]
MedicalResearch.com Interview with:
Alberto Pappo, M.D.
Member, Oncology; Director, Solid Tumor Division
St. Jude Children’s Research Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Pappo: Researchers have identified three distinct subtypes of childhood and adolescent tumors of pigment-producing skin cells called melanocytes. The subtypes have different genetic alterations and often different outcomes for patients. The findings should aid efforts to improve diagnosis and treatment of melanoma, which is the most common skin cancer in children and adolescents.
The study provides the most comprehensive analysis yet of the genetic alteration underlying pediatric melanoma, including the first genetic evidence that sun damage causes melanoma in children and adolescents as well as adults. Researchers used whole genome sequencing and other techniques to study the normal and cancer genomes of 23 young patients with a variety of melanocytic tumors, including conventional melanoma. Patients ranged in age from 9 months to 19 years old.
The melanoma subtypes in this study included conventional melanoma, which scientists showed was the same disease in children, adolescents and adults. More than 90 percent of pediatric conventional melanoma had DNA changes linked to sun damage.
23 Feb Wound Healing: Better Understanding of How Skin Cells Close Gaps
MedicalResearch.com Interview with:
Chwee Teck (C.T.) LIM PhD
Provost’s Chair Professor, Deputy Head, Department of Biomedical Engineering & Department of Mechanical Engineering
Principal Investigator, Mechanobiology Institute
Faculty Fellow, Singapore-MIT Alliance for Research & Technology (SMART) National University of Singapore
Medical Research: What is the background for this study? What are the main findings?
Professor Chwee Teck Lim: Epithelial cells have a natural tendency to close gaps and this feature plays a crucial role in many biological processes such as embryological development and wound healing. For example, skin does consist of epithelial cells that when wounded, will elicit closure to initiate healing. How epithelial cells close such gaps has always fascinated researchers from across many disciplines. It is generally accepted that two major mechanisms exist that underlie such a closure. The first is a "cell-crawling" mechanism wherein cells at the edge of the gap actively send protrusions or lamellipodia and use them as footholds to migrate over the gap. However, such a migration requires that the gap is conducive for cells to attach and form adhesions or footholds. The second mechanism is based on a coordinated contraction of multiple bundles of cellular cytoskeletal components (bundles of actin) in a manner similar to that of a "purse-string".
Despite many studies, it has always been difficult to understand and characterize these processes separately since most often they co-exist. In this study, we show that keratinocyte monolayers have a tendency to close circular non-adhesive gaps (gaps that have been coated with a polymer that does not allow cells to adhere or form foot-holds) through contraction of bundles of actin within cells at the edge of the gap. We find that such as closure is strongly affected by the size of the gap (gaps more than 150 um in diameter have a tendency to close only partially), curvature of the gap (gaps with high curvature show better closure), and strength of intercellular adhesion (poor intercellular adhesion completely inhibits closure of non-adhesive gaps).
17 Feb How Much Does Specialized Melanoma Screening Cost?
MedicalResearch.com Interview with: Caroline Watts| PhD Candidate Cancer Epidemiology and Services Research | Sydney School of Public Health The University of Sydney MedicalResearch: What is the background for this study? What are the main findings? Response: A clinic for people at high risk of melanoma was established at the Royal Prince Alfred Hospital, Sydney in 2006 to look at the impact of surveillance regime which included regular full body skin examination supported by dermoscopy and total body photography at 6 monthly intervals. If a suspicious lesion was identified, the lesion was either removed or sequential digital dermoscopy was performed and the patient returned in 3 months for review. This study aimed to estimate the costs associated with surveillance in this type of specilaised clinic. The mean number of clinic visits per year was 2.7 (95% CI, 2.5-2.8) for surveillance and 3.8 (95% CI, 3.4-4.1) for patients requiring surgical excisions. The mean annual cost per patient to the health system was A $882 (95% CI, A $783-$982) (US $599 [95% CI, US $532-$665]) and mean annual societal cost per patient (excluding health system costs) was A $972 (95% CI, A $899-$1045) (US $660 [95% CI, US $611-$710). Diagnosis of melanoma or non-melanoma skin cancer and frequent excisions for benign lesions in a relatively small number of patients was responsible for skewed health system costs.15 Feb Hand Dermatitis Increases In Health Care Workers Due To Hand Washing Measures
MedicalResearch.com Interview with: Dr Jill Stocks PhD, Research Fellow Centre for Occupational and Environmental Health, Centre for Epidemiology; NIHR Greater Manchester Primary Care Patient Safety Translational Research Centre, Centre for Primary Care Institute of Population Health, University of Manchester, UK. Medical Research: What is the background for this study? What are the main findings? Dr. Stocks: Reducing healthcare-associated infections has been a priority in the UK over recent decades; and this has been reflected in interventions and guidelines focussing on improving hygiene procedures. During 2004 to 2008 the Cleanyourhands campaign promoted hand hygiene in all NHS trusts. There was anecdotal evidence from dermatologists and occupational physicians that irritant contact dermatitis was on the increase in healthcare workers, and that it was caused by hand hygiene. We investigated whether or not there was an increase in the incidence of irritant contact dermatitis in healthcare workers due to hand hygiene or other types of hygiene coinciding with the interventions and guidelines promoting hygiene. We used reports made by dermatologists to the Occupational and Health reporting network, a voluntary surveillance scheme collecting reports of work-related ill-health. Trends in incidence of irritant contact dermatitis due to hygiene in healthcare workers were compared with trends in control groups (irritant contact dermatitis in workers with other jobs) using a quasi-experimental (interrupted time series) design. We found a 4.5 fold increase in irritant contact dermatitis due to hand hygiene and hygiene in general in healthcare workers between 1996 and 2012. The results also suggested a steepening of the increase in incidence during the rollout period of the Cleanyourhands campaign but the limitations of the data made this less clear cut.11 Feb Study Examines Malpractice Risk Of Mohs Surgery For Skin Cancer
MedicalResearch.com Interview with:
Omar A. Ibrahimi, M.D., Ph.D
Connecticut Skin Institute
Founding Medical Director
Stamford, CT 06905
www.ctskindoc.com
Medical Research: What is the background for this study? What are the main findings?
Dr. Ibrahimi: The delivery of healthcare in a efficient and cost effective fashion is one of the largest themes in medicine today. Malpractice lawsuits have steadily increased with the cost of healthcare delivery. Mohs surgery involves the surgical removal, the tissue analysis and the reconstruction of a skin cancer all in a single visit that bundles multiple procedures in a cost effective manner that is proposed to be the gold standard for treating certain skin cancers.
Information regarding malpractice involving Mohs surgery is lacking. The only previous study that has been done was a survey of Mohs surgeons looking at how many had been involved in lawsuits and the reasons for being involved. Our study examined a legal database to identify all the lawsuits involving Mohs surgery and skin cancer. We were surprised to find that the majority of lawsuits involved non-Mohs surgeons as the primary defendant, mostly due to a delay of or failure in diagnosis, cosmetic outcome issues, lack of informed consent, and a delay of or failure in referral to a Mohs surgeon.