Long-Term Neurocognitive Outcomes in Sagittal Synostosis: The Impact of Reoperation.

INTRODUCTION: Optimal age at surgery in nonsyndromic sagittal craniosynostosis continues to be debated. Previous reports suggest that earlier age at whole vault cranioplasty more frequently requires reoperation. It is unknown, however, whether reoperation affects neurocognitive outcome. This study examined the impact of reoperation on neurocognitive outcome in children with nonsyndromic sagittal craniosynostosis using comprehensive neurocognitive testing. METHODS: Forty-seven school-age children (age 5-16 years) with nonsyndromic sagittal craniosynostosis who underwent whole-vault cranioplasty were included in this analysis. Participants were administered a battery of standardized neuropsychological testing to measure neurocognitive outcomes. RESULTS: Thirteen of the 47 participants underwent reoperation (27.7%); 11 out of the 13 reoperations were minor revisions while 2 reoperations were cranioplasties. Reoperation rate was not statistically different between patients who had earlier surgery (at age ≤6 months) versus later surgery (at age >6 months) (P > 0.05). Nonreoperated patients who had only one later-in-life surgery did not perform statistically better than reoperated patients on any outcome measure of neurocognitive function, including IQ, academic achievement, visuomotor integration, executive function, and behavior. Comparing reoperated earlier surgery patients with nonreoperated later surgery patients, reoperated earlier surgery patients had higher full-scale and verbal IQ (P < 0.05), scored higher on word reading, reading comprehension, spelling, numerical operations, and visuomotor integration (P < 0.05), and had fewer indicators of suspected learning disabilities (P < 0.01) compared to nonreoperated later surgery patients. CONCLUSION: Reoperation rate after whole vault cranioplasty was 27.7%, with few cases of repeat cranioplasty (4.2% of all patients). Reoperation was not associated with worse neurocognitive outcome. Reoperated earlier surgery patients in fact performed better in IQ, academic achievement and visuomotor integration when compared to nonreoperated later surgery patients.

Nanoparticles in dermatologic surgery.

Nanotechnology is an emerging branch of science that involves the engineering of functional systems on the nanoscale (1-100 nm). Nanotechnology has been used in biomedical and therapeutic agents with the aim of providing novel treatment solutions where small molecule size may be beneficial for modulation of biologic function. Recent investigation in nanomedicine has become increasingly important to cutaneous pathophysiology, such as functional designs directed towards skin cancers and wound healing. This review outlines the application of nanoparticles relevant to dermatologic surgery.

Crisaborole 2% ointment for the treatment of intertriginous, anogenital, and facial psoriasis: A double-blind, randomized, vehicle-controlled trial.

BACKGROUND: Psoriasis of the intertriginous, anogenital, and facial regions remains a therapeutic challenge, with current algorithms lacking a topical agent that exhibits both high efficacy and minimal side effects. OBJECTIVE: To assess the safety and efficacy of crisaborole 2% ointment-a nonsteroidal phosphodiesterase 4 inhibitor-in the treatment of intertriginous, anogenital, and facial psoriasis. METHODS: A double-blind, randomized, vehicle-controlled trial was conducted in 21 participants. Participants were randomized 2:1 to receive 4 weeks of twice-daily treatment with either crisaborole 2% ointment (n = 14) or vehicle ointment (n = 7), followed by 4 weeks of open-label treatment with crisaborole 2% ointment. Disease severity was measured by using the Target Lesion Severity Scale (TLSS). RESULTS: After 4 weeks, participants in the crisaborole group demonstrated 66% improvement compared with 9% in the vehicle group (P = .0011). Participants in the crisaborole group continued to experience improvement through the open-label phase, demonstrating 81% lesional improvement by week 8, with 71% of these participants achieving clinical clearance. There were no adverse events. LIMITATIONS: The study was limited to a single tertiary care center and small sample size. CONCLUSION: Treatment with crisaborole 2% ointment was well-tolerated and led to clinical improvement in participants with intertriginous, anogenital, or facial psoriasis.

Objective Evaluation of Skin Sensitivity Across Fitzpatrick Skin Types.

Context: Skin sensitivity may be best defined as self-reported intolerance to application of skincare products. It is commonly believed that individuals with darker skin are generally less sensitive, while those lighter skin are more sensitive. However, there is little objective data correlating sensitivity with skin type or with objective measures of sensitivity. Objective: This study assessed Fitzpatrick skin type and self-reported perception of skin sensitivity. Design: A single-blinded, lactic acid sting test was performed on the medial cheeks, where patients were randomized to receive room temperature 10% lactic acid on the left or right cheek with water applied to the contralateral cheek as a control. Outcome Measures: Stinging was assessed 1 minute after application of test solution to one cheek using a visual analogue scale (VAS). Results: There was a statistically significant difference in self-reported skin sensitivity in patients with Fitzpatrick skin types 1-3 vs 4-6 (73.6% vs 46.5%; P= 0.006). Patients who had higher perceived sensitivity were more likely to have objectively measured sensitivity as well, across all skin types (P<0.01). When stratified by skin type, a numerically higher percentage of subjects with Fitzpatrick skin types 1-3 experienced objective sensitivity compared to subjects with skin types 4-6 (45.6% vs 27.9; P=0.058). Conclusions: Patients with self-perceived skin sensitivity were more likely to develop objective stinging compared to those who did not report sensitivity. Skin sensitivity can occur across all skin types, and patients should be asked about self-perceptions of sensitivity as it is likely an indicator of true sensitivity. J Drugs Dermatol. 2020;19(7): doi:10.36849/JDD.2020.5880.

Topical Treatment for the Management of Atopic Dermatitis

Atopic dermatitis affects up to 20% of children and continues to increase in prevalence. Effective disease control is aimed at decreasing symptoms and reducing the frequency of flares, which may be complicated by secondary bacterial infections. Although recent advances have produced a number of non-systemic treatment options, topical corticosteroids remain a fundamental component of treatment algorithms. J Drugs Dermatol. 2019;18(2 Suppl):s112-116.

Combination Use of Systemic Therapies in Psoriasis: Baseline Characteristics from the Corrona Psoriasis Registry

IMPORTANCE: There are increasing options for systemic combination therapy for psoriasis but a lack of literature around the characteristics of patients who are started on these regimens. OBJECTIVE: We aimed to determine how combination systemic therapy patients differ from monotherapy patients in their social, medical, or treatment history. DESIGN: This was a cross-sectional study of patients enrolled in the Corrona Psoriasis Registry. Descriptive characteristics were compared in biologic monotherapy and combination therapy groups. SETTING: The Corrona PsO registry is a prospective multicenter observational disease-based registry with patients recruited from 154 private and academic practice sites in the US and Canada with 373 participating dermatologists. PARTICIPANTS: Patients 18 years of age or older who enrolled in the Corrona Psoriasis Registry between April 2015 and March 2017 and initiated an eligible biologic therapy at the time of enrollment were included. EXPOSURES: Eligible biologic therapies included adalimumab, etanercept, infliximab, ixekizumab, secukinumab, and ustekinumab. Non-biologic and small molecule adjunctive therapies included acitretin, apremilast, CsA, and MTX. RESULTS: Patients on combination therapy were more likely to identify as black, to have Medicaid, and to report disabled work status. While combination therapy patients were more likely to have concomitant PsA, no major differences were seen in disease morphology, duration, IGA, PASI, or BSA affected at treatment initiation. CONCLUSIONS: Various demographic and socioeconomic factors are associated with use of combination systemic therapy compared to use of systemic monotherapy for psoriasis. An association with commonly used disease severity indices was not observed. RELEVANCE: An understanding of which patients are more likely to be prescribed combination systemic therapy will provide important context for long-term efficacy and safety data as they become available.

Actinic Keratosis: Current Therapies and Insights Into New Treatments

Actinic keratosis (AK) develops on chronically sun-exposed skin and constitutes one of the most common diseases managed by dermatologists. The incidence of AKs continues to rise among aging as well as younger sun damaged populations worldwide, underscoring the importance of effective therapy options. Various treatments are available, including light-based therapies, topical therapies, and destructive therapies. Herein, we review the current management options for AKs and discuss emerging therapeutic agents. J Drugs Dermatol. 2019;18(5 Suppl 1):s161-166.

Analysis of Airway and Midface in Crouzon Syndromes.

BACKGROUND: Crouzon syndrome is associated with severe respiratory impairment of the upper airway due in part to midfacial dysmorphology. We calculated the distinctive nasal diameter and pharyngeal airway volume in patients with Crouzon syndrome and compared them with age-matched control subjects. METHODS: Children with computed tomography scans in the absence of surgical intervention were included. Computed tomography scans were digitized and manipulated using Surgicase CMF (Materialise). Craniometric data relating to the midface and airway were collected. For all linear measurements, mean percent increases or decreases were calculated relative to the size of control subjects, and volumetric assessment of the airway was tabulated. Statistical analysis was performed using t test. RESULTS: Twenty-six computed tomography scans were included (control n = 17, Crouzon n = 9). All children were in early mixed dentition. Pharyngeal airway volume was decreased in patients with Crouzon syndrome relative to control subjects by 46% (P = 0.003). The distance from the posterior tongue to the posterior pharyngeal wall decreased 31% when comparing the Crouzon group versus the control (P = 0.04). CONCLUSIONS: Three-dimensional analysis revealed notably decreased pharyngeal and nasal airway volumes in patients with Crouzon syndrome, but nasal bone tissue and soft tissue measurements showed very little change between patients and control subjects.

The Efficacy and Safety of Azelaic Acid 15% Foam in the Treatment of Facial Acne Vulgaris.

BACKGROUND: Azelaic acid demonstrates anti-inflammatory, anti-oxidative, anti-comedogenic, and anti-microbial effects. Azelaic acid 20% cream is currently approved for the treatment of acne vulgaris, and azelaic acid 15% foam has recently been approved for rosacea. Given the favorable tolerability profile of foam preparations, it is reasonable to assume that azelaic acid 15% foam could serve as a viable treatment option for facial acne. OBJECTIVE: To examine the efficacy and safety of azelaic acid 15% foam in the treatment of moderate-to-severe facial acne Methods: Twenty subjects with moderate-to-severe facial acne vulgaris were enrolled in this two-center, open-label pilot study. All study subjects were treated with azelaic acid 15% foam for 16 weeks. Efficacy analyses were based on the change in facial investigator global assessment (FIGA) and changes in total, inflammatory, non-inflammatory lesion counts between baseline and week 16. RESULTS: There was a significant reduction in FIGA scores from baseline to week 16 (p = .0004), with 84% of subjects experiencing at least a 1 grade improvement, and 63% of subjects achieving a final grade of Clear or Almost Clear. All subjects experienced reductions in inflammatory and total lesion counts by week 16, and 89% of subjects experienced reductions in non-inflammatory lesions. Azelaic acid 15% foam was well tolerated, with almost all instances of erythema, dryness, peeling, oiliness, pruritus, and burning being of mild or trace degree, and most adverse effects resolving by the end of the study. CONCLUSION: Azelaic acid 15% foam is effective and safe in the treatment of facial acne vulgaris. Given the convenience of foam vehicles, azelaic acid 15% foam should be considered as a viable treatment option for this condition. J Drugs Dermatol. 2018;17(6):641-645.

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What Lies Beneath the Face Value of a BOX WARNING: A Deeper Look at Brodalumab.

Brodalumab, a fully human antibody of the interleukin-17 receptor, is highly effective in the treatment of moderate-to-severe plaque psoriasis. However, based on safety signals identified in clinical trials, brodalumab carries a boxed warning regarding possible risks of suicidal ideation and behavior (SIB). The validity of this link remains controversial, especially in the context of the psoriasis population as well as clinical trial data from other recently approved treatments. Herein, we critically examine the association between brodalumab and SIB. J Drugs Dermatol. 2018;17(8 Suppl):s29-34.

Normalization of Speech Processing After Whole-Vault Cranioplasty in Sagittal Synostosis.

BACKGROUND: Neurocognitive studies have found impairments in language-related abilities in nonsyndromic craniosynostosis, highlighting clinical importance of early language processing. In this study, neural response to speech sounds in infants with nonsyndromic sagittal craniosynostosis (NSC) is compared, preoperatively and postoperatively, using event-related potentials (ERPs) to objectively characterize development in language processing. METHODS: Electroencephalogram was recorded while 39 infants (12 NSC and 27 controls; ages 73-283 days) listened to the Hindi dental /(Equation is included in full-text article.)a/ and retroflex /da/ phonemes (non-native phonemic discrimination task). The mismatch negativity (MMN) ERP was extracted as the peak amplitude of the largest negative deflection in the difference wave over 80 to 300 milliseconds poststimulus. Differences in MMN were analyzed using repeated measures analysis of variance. RESULTS: The MMN amplitude was attenuated in the infants with NSC preoperatively compared with controls (P = 0.047). A significant region by group interaction (P = 0.045) was observed, and infants with NSC displayed attenuated MMN in the frontal electrodes compared with controls (P = 0.010). Comparing the preoperative and postoperative MMN, a time by group interaction trend (P = 0.070) was observed. Pair-wise comparisons showed a trend for increase in MMN amplitude from preoperatively to postoperatively in the infants with NSC (P = 0.059). At the postoperative time point, infants with NSC showed no significant difference in MMN from controls (P = 0.344). CONCLUSION: Infants with NSC demonstrated atypical neural response to language preoperatively. After undergoing surgery, infants with NSC showed increased MMN amplitude which was not significantly different from controls. These findings support the idea that whole vault cranioplasty may improve neurocognitive outcomes in sagittal craniosynostosis.

A Comparative Study to Evaluate Epidermal Barrier Integrity of Psoriasis Patients Treated With Calcipotriene/Betamethasone Topical Suspension Versus Betamethasone Dipropionate 0.05% Lotion.

BACKGROUND: Topical corticosteroids are known to impair the epidermal barrier, even after short-term use, whereas topical vitamin D analogues can have a reparative effect. Combination products using corticosteroids and vitamin D analogues have gained popularity in recent years and may provide a means to minimize skin atrophy in patients treated with topical corticosteroids. OBJECTIVE: To compare epidermal barrier function and cutaneous atrophy after 4 weeks of calcipotriene 0.005% and betamethasone dipropionate 0.064% topical suspension (Taclonex® TS) versus betamethasone dipropionate 0.05% lotion (Diprosone®). METHODS: Ten subjects with moderate plaque psoriasis were enrolled. Patients were randomized to apply calcipotriene 0.005%/betamethasone dipropionate 0.064% once daily to psoriasis plaques on one side of the body and betamethasone dipropionate 0.05% lotion twice daily to plaques on the other side. Biopsies were performed at baseline and after four weeks of treatment to evaluate for epidermal and dermal changes. RESULTS: Treatment with betamethasone lotion resulted in significant decreases in epidermal thickness and dermal thickness. In contrast, treatment with calcipotriene/betamethasone did not lead to significant decreases in epidermal thickness or dermal thickness. Comparing betamethasone and calcipotriene/betamethasone, there was a significantly greater reduction in epidermal thickness with betamethasone lotion versus calcipotriene/betamethasone (P less than .0001). Relative differences in dermal thickness and transepidermal water loss (TEWL) did not reach statistical significance. CONCLUSION: This study is the first to demonstrate that treatment of plaque psoriasis with a combination topical corticosteriod and calcipotriene product results in greater preservation of the skin layers relative to topical corticosteroid use alone. These results hold important ramifications for minimizing cutaneous atrophy in patients receiving treatment with topical corticosteroid .

Assessment of Efficacy and Irritation of Ingenol Mebutate Gel 0.015% Used With or Without Dimethicone Lotion for Treatment of Actinic Keratosis on the Face.

Background: Ingenol mebutate gel 0.015% provides high clearance rates for actinic keratosis (AK) on the face and scalp but causes transient local skin responses (LSRs).

Objective: This study sought to determine whether the application of 1% dimethicone would decrease ingenol mebutate-associated LSRs and/or affect efficacy during the treatment of multiple AKs on the face.

Methods: Ingenol mebutate gel 0.015% was applied for 3 days to two 25 cm2 areas, each containing 3 to 8 AKs on the face of each subject, followed by application of 1% dimethicone lotion in an investigator-blinded manner to one randomly selected AK-containing area until LSRs were no longer present.

Results: In total, 20 subjects were enrolled and completed the study. Topical 1% dimethicone lotion applied during and after treatment of facial AK with ingenol mebutate gel 0.015% reduced mean total LSR scores at days 8 and 15 compared with ingenol mebutate gel only, although the difference was not statistically significant. Efficacy was equivalent between the two treatment arms.

Limitations: The study evaluated a relatively small number of subjects, all of whom were white.

Conclusions: The application of 1% dimethicone following ingenol mebutate gel 0.015% produced a trend toward lower severity of some LSRs, with no difference in efficacy.

J Drugs Dermatol. 2017;16(5):432-436.

Direct brain recordings reveal impaired neural function in infants with single-suture craniosynostosis: a future modality for guiding management?

BACKGROUND: Patients with single-suture craniosynostosis (SSC) are at an elevated risk for long-term learning disabilities. Such adverse outcomes indicate that the early development of neural processing in SSC may be abnormal. At present, however, the precise functional derangements of the developing brain remain largely unknown. Event-related potentials (ERPs) are a form of noninvasive neuroimaging that provide direct measurements of cortical activity and have shown value in predicting long-term cognitive functioning. The current study used ERPs to examine auditory processing in infants with SSC to help clarify the developmental onset of delays in this population. METHODS: Fifteen infants with untreated SSC and 23 typically developing controls were evaluated. ERPs were recorded during the presentation of speech sounds. Analyses focused on the P150 and N450 components of auditory processing. RESULTS: Infants with SSC demonstrated attenuated P150 amplitudes relative to typically developing controls. No differences in the N450 component were identified between untreated SSC and controls. CONCLUSIONS: Infants with untreated SSC demonstrate abnormal speech sound processing. Atypicalities are detectable as early as 6 months of age and may represent precursors to long-term language delay. Electrophysiological assessments provide a precise examination of neural processing in SSC and hold potential as a future modality to examine the effects of surgical treatment on brain development.

Symptomatic obstruction of the brachiocephalic and left subclavian arteries obscured by aortic stenosis.

Stenosis or occlusion of the brachiocephalic artery represents an uncommon cause of cerebrovascular insufficiency. We report a patient with combined brachiocephalic and left subclavian obstruction with clinical manifestations of lightheadedness, syncope, and left-sided weakness who remained misdiagnosed essentially because of symmetrical pressures in the upper extremities. Aortic valve replacement for aortic stenosis failed to provide symptomatic relief. Eventual stenting of the brachiocephalic trunk resolved the patient's symptoms. Our report highlights the diagnostic challenges in this case of bilateral supraaortic vessel disease and shows that equal upper extremity pressures do not rule out brachiocephalic artery obstruction.

Liver laceration from a diaphragmatic suture in minithoracotomy mitral valve repair.

Mitral valve operations are increasingly performed through minimally invasive approaches such as the right anterior minithoracotomy. To facilitate exposure with this technique, a diaphragmatic suture may be implemented. We describe a liver laceration caused by the diaphragmatic suture in minithoracotomy mitral repair and its successful nonoperative management with arterial embolization.

The "free" right internal thoracic artery: a versatile and durable conduit.

BACKGROUND: Despite its potential advantages, the right internal thoracic artery (RITA) is used as a conduit in only 4% of coronary revascularizations. To broaden its application, we frequently use the RITA as a free graft. In this study, we review our experience with the RITA as an in situ and free graft. METHODS: We reviewed the perioperative outcomes and angiographic patency rates of 479 consecutive patients who underwent RITA grafting between January 1987 and December 2011. RESULTS: The RITA was harvested free (FRITA) in 380 patients (79%) and in situ in 99 (21%). The predominant target for the in situ RITA was the right coronary system (79%). The predominant targets for the FRITA were divided between the right (54%) and left coronary systems (46%). There was no perioperative mortality. Mean follow-up was 10 years. Perioperative complications included myocardial infarction (0.4%), sternal nonunions (0.4%), and reoperation for hemorrhage (0.6%). Coronary angiograms were performed in symptomatic patients (17%) after a median of seven years. FRITA patency rates at five, 10, and 15 years were 100%, 95%, and 95%, respectively, comparable to the left internal thoracic artery patency rates and superior to those of saphenous vein graft. Survival rates of FRITA patients at 10, 15, and 20 years were 92%, 89%, and 76%, respectively. CONCLUSION: The FRITA graft reaches all distal coronary vessels and is associated with excellent patency and survival rates. Its application in coronary revascularization vastly expands the benefits of internal thoracic artery grafting.

Does an elevated bony ridge along the course of the metopic suture equal metopic synostosis? Implications for management.

Metopic synostosis represents an increasingly prevalent form of nonsyndromic craniosynostosis. Premature fusion of the metopic suture classically results in trigonocephaly, hypotelorism, temporal narrowing, and a pronounced midline forehead ridge. However, as varying degrees of skull deformity exist, there is confusion regarding the appropriate management for an infant with a metopic ridge. We report on a 2-month-old infant with clinical manifestations of metopic synostosis but with a patent metopic suture documented on computed tomography scan. We examine the implications for management related to fusion of the suture, age of the patient, and severity of the head deformity.