Pigmented Lesions of the Oral Cavity.

Pigmented lesions are a common finding in the oral cavity. Oral pigmented lesions may range from solitary to multiple, pinpoint to diffuse, and have a variety of clinical implications. Nearly all solitary pigmented lesions require a biopsy to rule out mucosal melanoma. Oral mucosal melanoma has a grim prognosis and early discovery is of utmost importance. Multiple pigmented lesions in the oral cavity may indicate a systemic condition about which the patient may not be aware. The presentation and management of these various lesions is the focus of this article.

CGRP, adrenomedullin and adrenomedullin 2 display endogenous GPCR agonist bias in primary human cardiovascular cells.

Agonist bias occurs when different ligands produce distinct signalling outputs when acting at the same receptor. However, its physiological relevance is not always clear. Using primary human cells and gene editing techniques, we demonstrate endogenous agonist bias with physiological consequences for the calcitonin receptor-like receptor, CLR. By switching the receptor-activity modifying protein (RAMP) associated with CLR we can "re-route" the physiological pathways activated by endogenous agonists calcitonin gene-related peptide (CGRP), adrenomedullin (AM) and adrenomedullin 2 (AM2). AM2 promotes calcium-mediated nitric oxide signalling whereas CGRP and AM show pro-proliferative effects in cardiovascular cells, thus providing a rationale for the expression of the three peptides. CLR-based agonist bias occurs naturally in human cells and has a fundamental purpose for its existence. We anticipate this will be a starting point for more studies into RAMP function in native environments and their importance in endogenous GPCR signalling.

The role of hypothalamus-pituitary-adrenal (HPA)-like axis in inflammatory pilosebaceous disorders.

Skin is the largest peripheral endocrine organ and functions as a hormone target and endocrine gland. A cutaneous hypothalamus-pituitary-adrenal (HPA)-like axis enables the skin to respond to stress and regulates its steroidogenic activity. The pilosebaceous unit is a site for production and metabolism of a number of steroid hormones, including stress and sex hormones. This is an overview of the important role that the cutaneous HPA-like-axis plays in the pathogenesis and treatment of inflammatory pilosebaceous disorders, including acne, rosacea, seborrheic dermatitis, and hidradenitis suppurativa.

Leading Change in Nurse Bedside Shift Report.

Nurse bedside shift report (NBSR) focuses on patient-centered care, and implementing the change starts with buy-in from management and a strong educational platform. Based on that platform, nurse champions grow to help foster education to their peers. Education and tools were provided to Registered Nurses and Certified Nursing Assistants. The pilot was implemented in 2 phases onto the Medical Oncology unit, and an incentive program ran concurrently. A prepilot revealed the following projected barriers: time to complete NBSR, concerns with the Health Insurance Portability and Accountability Act, attending to patient needs, and being able to perform NBSR.

Receptor component protein, an endogenous allosteric modulator of family B G protein coupled receptors.

Receptor component protein (RCP) is a 148 amino acid intracellular peripheral membrane protein, previously identified as promoting the coupling of CGRP to cAMP production at the CGRP receptor, a heterodimer of calcitonin receptor like-receptor (CLR), a family B G protein-coupled receptor (GPCR) and receptor activity modifying protein 1 (RAMP1). We extend these observations to show that it selectively enhances CGRP receptor coupling to Gs but not Gq or pERK activation. At other family B GPCRs, it enhances cAMP production at the calcitonin, corticotrophin releasing factor type 1a and glucagon-like peptide type 2 receptors with their cognate ligands but not at the adrenomedullin type 1 (AM1), gastric inhibitory peptide and glucagon-like peptide type 1 receptors, all expressed in transfected HEK293S cells. However, there is also cell-line variability as RCP did not enhance cAMP production at the endogenous calcitonin receptor in HEK293T cells and it has previously been reported that it is active on the AM1 receptor expressed on NIH3T3 cells. RCP appears to behave as a positive allosteric modulator at coupling a number of family B GPCRs to Gs, albeit in a manner that is regulated by cell-specific factors. It may exert its effects at the interface between the 2nd intracellular loop of the GPCR and Gs, although there is likely to be some overlap between this location and that occupied by the C-terminus of RAMPs if they bind to the GPCRs.

Quantification of ultraviolet (UV) radiation in the shade and in direct sunlight.

Ultraviolet (UV) radiation is associated with negative health effects, including sun damage and skin cancer. The purpose of this study is to compare the protective effects of the shade provided by a sun umbrella versus that provided by a tree. Sun sensors that register the level and dose of UV radiation were placed in the shade and in direct sunlight. Measurements were recorded every half hour between the hours of 12:30 p.m. and 3:00 p.m. in Sacramento, California. The results suggest that the level of UV radiation in the shade is not zero. The sensors located in tree shade indicated that over 5% of UV radiation was detected in the shade. The sensors located in sun-umbrella shade showed that greater than 17% of UV radiation reached the shade. The sun sensors used in our study collected UV radiation data relevant to UV index; however, they did not differentiate between UVA, UVB, visible, and infrared light. The amount of UV radiation detected in the shade is not zero, thus regular sunscreen use and other sun protective practices should be followed to reduce the risk of sun damage and skin cancer.

Ulcerated Lesions of the Oral Mucosa: Clinical and Histologic Review.

Ulcerated lesions of the oral cavity have many underlying etiologic factors, most commonly infection, immune related, traumatic, or neoplastic. A detailed patient history is critical in assessing ulcerative oral lesions and should include a complete medical and medication history; whether an inciting or triggering trauma, condition, or medication can be identified; the length of time the lesion has been present; the frequency of episodes in recurrent cases; the presence or absence of pain; and the growth of the lesion over time. For multiple or recurrent lesions the presence or history of ulcers on the skin, genital areas, or eyes should be evaluated along with any accompanying systemic symptoms such as fever, arthritis, or other signs of underlying systemic disease. Biopsy may be indicated in many ulcerative lesions of the oral cavity although some are more suitable for clinical diagnosis. Neoplastic ulcerated lesions are notorious in the oral cavity for their ability to mimic benign ulcerative lesions, highlighting the essential nature of biopsy to establish a diagnosis in cases that are not clinically identifiable or do not respond as expected to treatment. Adjunctive tests may be required for final diagnosis of some ulcerated lesions especially autoimmune lesions. Laboratory tests or evaluation to rule out systemic disease may be also required for recurrent or severe ulcerations especially when accompanied by other symptoms. This discussion will describe the clinical and histopathologic characteristics of a variety of ulcerated lesions found in the oral cavity.

Use of 5-0 Fast Absorbing Gut versus 6-0 Fast Absorbing Gut during cutaneous wound closure on the head and neck: A randomized evaluator-blinded split-wound comparative effectiveness trial.

BACKGROUND: Absorbable suture material (Fast Absorbing Gut [FG], Ethicon, Somerville NJ) is often used for patient convenience; however, the optimal diameter of FG sutures is debatable. OBJECTIVE: To determine whether the use of 6-0 FG during repair of linear cutaneous surgery wounds on the head and neck improves scar cosmesis compared with the use of 5-0 FG. METHODS: This was a prospective, randomized, split-scar intervention in patients undergoing repair of linear cutaneous wounds on the head and neck. The scar was assessed 3 months after surgery via the Physician Observer Scar Assessment Scale (POSAS), a validated instrument. RESULTS: The difference in the sum of the POSAS component scores for 6-0 FG (12.03) compared with that for 5-0 FG (13.11) was not statistically significant (P = .26). Observer overall opinion was similar for both interventions, at 2.49 for 6-0 FG vs 2.64 for 5-0 FG (P = .54). The difference in the number of complications in the 5-0 FG group (15) vs the 6-0 FG group (10) was not statistically significant (P = .40). LIMITATIONS: Single-center study with wounds limited to the head and neck in white individuals, with a predominance of men. CONCLUSION: For linear repair of cutaneous wounds, 6-0 FG was not statistically different for cosmetic outcomes, scar width, and complications compared with 5-0 FG.

Dietary supplementation with turmeric polyherbal formulation decreases facial redness: a randomized double-blind controlled pilot study.

BACKGROUND: Facial redness is multifactorial in nature and may be a sign of many different conditions, including rosacea, photo damage and flushing. Herbal medicines have been used for thousands of years to treat a variety of dermatological conditions. Turmeric (Curcuma longa) and its constituents have been shown to mediate dilation and constriction of peripheral arterioles and have demonstrated anti-oxidant, anti-inflammatory and wound-healing properties. OBJECTIVE: To investigate the effects of turmeric and turmeric-containing polyherbal combination tablets versus placebo on facial redness. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: This was a prospective, double-blind, randomized pilot study. Thirty-three healthy participants were recruited from the dermatology clinic at the University of California, Davis and nearby community from 2016 to 2017. Thirty participants were enrolled, and 28 participants completed the study. The enrolled participants were randomized to receive one of three interventions (placebo, turmeric or polyherbal combination tablets) and were told to take the intervention tablets by mouth twice daily for 4 weeks. Facial redness was assessed at baseline and 4 weeks after intervention by clinical grading and by image-based analysis. MAIN OUTCOME MEASURES: The primary outcome measure was image-based facial quantification of redness using a research camera and software analysis system. The investigators performed an intention-to-treat analysis by including all subjects who were enrolled in the trial and received any study intervention. Differences were considered statistically significant after accounting for multiple comparisons. Effect sizes for clinical grading were calculated with a Hedges' g where indicated. RESULTS: Twenty-eight participants completed the study and there were no reported adverse events. Based on clinical grading, facial redness intensity and distribution down trended in the polyherbal combination group after 4 weeks (P = 0.1). Under photographic image analysis, the polyherbal combination group had a significant decrease in redness of 40% compared to baseline (P = 0.03). The placebo and turmeric groups had no statistically significant changes in image analysis-based facial redness. CONCLUSION: Polyherbal combination tablet supplementation improved facial redness compared to the turmeric or placebo. Overall, our findings suggested further investigations into the effects of turmeric and polyherbal formulations in skin conditions associated with facial redness would be warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03065504.

Symmetrical palatal fibromatosis: Five new cases and a review of the literature.

OBJECTIVE: To present five cases of symmetrical palatal fibromatosis (SPF), a lesion reported very rarely in the English language literature, under more than a dozen different names, and to recommend the most appropriate name. METHODS: Five SPF cases are characterized with a literature review. RESULTS: Three females and two males, aged 20-39 years, presented with bilateral, symmetrical, asymptomatic, sessile, moderately firm, or soft (n = 2) masses of the lateral posterior hard palate; two were isolated to the tuberosities. All masses were normal in color, with smooth, non-ulcerated surfaces and occasional surface nodularity. Underlying bone was radiographically normal, and adjacent teeth were asymptomatic. All masses originated from supra-periosteal tissues over palatal bone, only secondarily extending to gingivae and/or crestal tuberosity. Cases were present between 4 months and 15 years, with no familial or environmental etiologies identified. Histopathologically, masses were comprised of dense, avascular fibrous tissue with scattered thick bands of collagen. Surface epithelium showed occasional long, thin, sometimes pointed rete processes, and subepithelial stroma contained scattered large, angular fibroblasts. Conservative surgical excision appeared curative in all cases. CONCLUSIONS: The present investigators propose SPF as the most accurate name for this rare entity.

Readability of information on colonoscopy preparation on the internet.

Background: The incidence of colorectal cancer (CRC) has decreased in recent years, due in large part to increased screening, particularly through colonoscopy. This study aimed to examine the level of readability of information on colonoscopy preparation written on 100 websites that were found via an internet search. Methods: In this cross-sectional study, the content of the first 100 websites in English found via an internet search were analyzed using established readability scales. Websites were compared based on whether they had a commercial or non-commercial URL extension. Results: The majority of websites were found to have information of a difficult reading level. Less than 10% of websites had an easy reading level. Readability did not differ significantly based on URL extension. Conclusion: The information currently posted on the internet regarding preparation for colonoscopy is written at a difficult reading level. If information presented was both accurate and easier to read, it could benefit a greater proportion of the general public and help inform decisions about preparing for a colonoscopy.

Utility of Routine Surveillance Imaging for Hodgkin Disease following Autologous Transplant: Experiences from a Single Institution.

BACKGROUND: Surveillance scans performed after autologous stem cell transplant (auto-HCT) for patients with Hodgkin disease (HD) have no proven survival benefit. METHODS: We studied survival differences among patients with HD after auto-HCT whose recurrences were detected on clinical history and exam, versus those detected on routine surveillance scan. RESULTS: Among the 98 patients with HD that underwent auto-HCT from 2000 to 2014 at our institution, 30 relapsed, of which 21 were detected radiologically and 9 clinically. There were no statistically significant differences in patient characteristics between the 2 groups. The median time to progression was 118 days for the clinical cohort and 284 days for the radiological cohort (p = 0.05). Median overall survival (OS) was 728 days for the clinical cohort, and was not reached for the radiological cohort (p = 0.02). DISCUSSION: In our review, most patients with HD after auto-HCT were diagnosed radiologically. Patients whose relapse was diagnosed clinically were likely to be detected earlier and have a shorter OS. Patients with aggressive disease may be detected when clinically relevant, regardless of scanning. Routine scanning may not be necessary in the majority of patients with HD following auto-HCT.

Novel Route of Sirolimus Administration in a Neonate.

A term newborn presented with widespread cutaneous erythematous to bluish lesions since birth. He had extensive lesions in the gastrointestinal tract, brain, retina, heart, and bones. He also developed an intestinal perforation due to erosion of an intestinal lesion. Due to his critical status and clinical presentation, he was initially diagnosed with multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT), and sirolimus treatment was initiated. Sirolimus was given by buccal route in this nonfeeding patient. Therapeutic serum levels were obtained comparable to enteral administration. Buccal mucosa was an effective novel route of sirolimus administration in this patient.

Utility of routine surveillance imaging for diffuse large B-cell lymphoma post autologous transplant: A single center experience.

Surveillance scans after autologous stem cell transplant (auto-HCT) for patients with relapsed/refractory (RR) diffuse large B Cell lymphoma (DLBCL) have no proven survival benefit. We studied survival differences among patients with RR DLBCL post auto-HCT whose recurrences were detected clinically versus with routine surveillance imaging. Among the 139 patients with RR DLBCL that underwent auto-HCT from 2000 to 2014 at our institution, 37 relapsed: 21 clinical and 16 radiological. The median time to progression was 167 days for the clinical cohort and 565 days for the radiological cohort (p = 0.03), and median overall survival (OS) was 587 days and not reached, respectively (p = 0.006). Most patients with relapsed DLBCL after auto-HCT were diagnosed clinically and were likely to be detected earlier and have a shorter OS. Relapse in patients with aggressive disease will likely be detected when clinically apparent, and the outcome of these patients is independent of the way the relapse is diagnosed. Thus, universal scanning after auto-HCT appears to have little benefit.

Targeted treatments for hidradenitis suppurativa: a review of the current literature and ongoing clinical trials.

PURPOSE: Targeted, immune-modulating drugs are at the forefront of therapy for HS, and a comprehensive clinical trial registry is needed to facilitate data pooling and clinical efficacy comparison. MATERIALS AND METHODS: A systematic review of the ClinicalTrials.gov database was searched for planned, in-progress, completed, or terminated trials investigating the effect of targeted biologic therapies for hidradenitis suppurativa (HS). When results of RCTs were not available, case reports or series were included. RESULTS: Inflammatory mediators that are targeted by biologic agents include tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), IL-17, IL-12, IL-23, phosphodiesterase 4 (PDE4), lymphocyte function-associated antigen 1 (LFA-1), and complement component 5a (C5a). Clinical efficacy was measured by reduction in Sartorius score, Hidradenitis Suppurativa Clinical Response (HiSCR), Dermatology Life Quality Index (DLQI), or pain Visual Analog Scale (VAS). TNF inhibitors (adalimumab, etanercept, and infliximab), IL-1 receptor antagonist (Anakinra), IL-17A inhibitor (secukinumab), IL-12/23 inhibitor (ustekinumab), and PDE4 inhibitor (apremilast) show promise due to statistically significant improvements in disease severity. CONCLUSIONS: Currently, adalimumab is the only FDA-approved biologic available for the treatment of HS. However, results from trials of other biologic agents targeting downstream mediators are promising. Large-scale, randomized, placebo-controlled trials in patients with skin of color, as well as weight-based dosing trials, are needed.

Potential Role of Curcumin Against Biofilm-Producing Organisms on the Skin: A Review.

Turmeric root (Curcuma longa) is predominantly used as a spice, but has also long been known to possess antimicrobial, analgesic, antiinflammatory, and anticancer properties. One predominant group of active compounds in turmeric are curcuminoids, namely bright yellow-pigmented curcumin. While modern science has yet to fully investigate the therapeutic claims of turmeric and its derivatives, results have proven promising in decreasing pain and inflammation in arthritis, improving insulin sensitivity in diabetes, and even curing a variety of infections. The purpose of this review is to discuss the potential for curcumin as an agent against microbial infections, with a special focus on the skin and in the development of bacterial biofilms. Curcumin has demonstrated bactericidal efficacy against a variety of infections when administered with antibiotics in several clinical studies, with consistent antimicrobial activity demonstrated in vitro, as well as in urinary tract infections, gingival infections, and chronic wound infections. Hypothesized mechanisms of action include curcumin's ability to perturb bacterial membranes, disturb protofillament assembly, and even impair bacterial virulence factors. Further investigation is needed to fully understand which organisms are most susceptible to the effects of curcumin and how curcumin can be implemented in dermatology to treat skin conditions such as chronic wounds and acne vulgaris. Copyright © 2017 John Wiley & Sons, Ltd.

The Role of Polyphenols in Rosacea Treatment: A Systematic Review.

OBJECTIVES: Various treatment options are available for the management of rosacea symptoms such as facial erythema, telangiectasia, papules and pustules, burning, stinging, and itching. Botanical therapies are commonly used to treat the symptoms. The objective of this review is to evaluate the use of polyphenols in rosacea treatment. DESIGN: PubMed, Embase, Biosis, Web of Knowledge, and Scopus databases were systematically searched for clinical studies evaluating polyphenols in the management of rosacea. RESULTS: Of 814 citations, 6 met the inclusion criteria. The studies evaluated licochalcone (n = 2), silymarin (n = 2), Crysanthellum indicum extract (n = 1), and quassia extract (n = 1). The studies only evaluated topical formations of stated polyphenols. Main results were summarized. CONCLUSIONS: There is evidence that polyphenols may be beneficial for the treatment of rosacea symptoms. Polyphenols appear to be most effective at reducing facial erythema and papule and pustule counts. However, studies included have significant methodological limitations and therefore large-scale, randomized, placebo-controlled trials are warranted to further assess the efficacy and safety of polyphenols in the treatment of rosacea.