Efficacy of 785-nm Picosecond Titanium Sapphire Laser for Treatment of Brown Nevus of Ota Lesions in FST II-V: A Retrospective Analysis.

BACKGROUND: Nevus of Ota (NOTA) is a dermal melanocytosis acquired in early childhood or pregnancy. Given their color variability, NOTA often require a combination of wavelengths for successful treatment. Quality-switched lasers have consistently shown efficacy in targeting dermal pigment, while picosecond lasers (PSLs) are an emerging technology for pigmentary disorders. OBJECTIVE: To further elucidate its efficacy, the authors conducted a retrospective review of 17 patients with NOTA treated with a 785-nm PSL for brown NOTA lesions between 2021 and 2023. MATERIALS AND METHODS: The primary end point analyzed clinical improvement based on before and after photography reviewed by 3 board-certified dermatologists using a five-point visual analog scale. RESULTS: Seventeen patients of Fitzpatrick skin types (FSTs) II to V, ranging from ages 14 to 38 years, were included in this study. Patients were treated for an average of 3.2 sessions in 2 to 3-month intervals. Visual analog scale scores demonstrated a mean clearance of 51% to 75%. No pigmentary alterations were noted. CONCLUSION: Because NOTA is common in higher FSTs, the authors believe that the 785-nm PSL is an excellent treatment option for brown NOTA in these skin types. This study highlights the need for further investigation to determine optimal treatment parameters for the color-based laser treatment approach for NOTA.

The 730 nm picosecond titanium sapphire laser for treatment of café-au-lait macules in all skin types.

OBJECTIVES: Café-au-lait macules (CALM) are benign birthmarks presenting as uniformly pigmented, well demarcated, brown patches that can be distressing to patients, especially when located in cosmetically sensitive areas. As with all pigmentary lesions in skin of color patients, CALMs have been particularly challenging to treat. Here we present the first case series characterizing treatment parameters and clinical outcomes utilizing the 730-nm picosecond titanium sapphire laser for the treatment of CALMs. This device provides an additional safe and effective treatment option for these challenging cases. METHODS: We performed a retrospective review of patients treated at a single institution between April 2021 and December 2023. Clinical photographs were graded by 3 outside board-certified dermatologists using a 5-point visual analog scale. RESULTS: Fourteen patients (age range: 10 months-66 years, mean age: 27.4 years, Fitzpatrick skin types II-VI) were treated for CALM on the face (11) or body (3). On average, patients received 4.3 treatments, with treatment intervals ranging from 4 to 40 weeks. Treatment remains ongoing with the 730-nm picosecond laser for eight patients. Overall, patients were rated to have a mean improvement of 26%-50%. Two patients (FST III and VI) achieved 100% clearance after 4-5 treatment sessions. Our study included four patients whose CALM were of the smooth bordered "coast of California" subtype, three of whom had a mean improvement rating of only 1%-25%. The fourth patient had near complete resolution. Follow up for these patients has ranged from 6 weeks to 1.5 years. Of the patients treated, one patient experienced transient post-inflammatory hyperpigmentation and another transient post-inflammatory hypopigmentation, while a third patient experienced mild persistent guttate hypopigmentation. Three patients experienced partial recurrence indicating that maintenance treatments may be needed in some patients. CONCLUSION: The 730-nm picosecond titanium sapphire laser is a safe and efficacious treatment option, in the right morphologic setting, to improve the cosmetic appearance of CALMs in a wide range of ages and skin types. To our knowledge, this is the first reported treatment of CALMs with picosecond lasers in FST V and VI patients. Our study also supports prior studies which have found that CALM with smooth-bordered "coast of California" morphology have a poor response to laser therapy as compared to those with jagged or ill-defined bordered "coast of Maine" morphology.

Treatment of Nevus of Ota in Black patients with the 1064 nm QS or picosecond laser and nonablative fractional photothermolysis.

OBJECTIVES: Nevus of Ota is a benign melanocytic lesion that presents as a unilateral blue gray to brown facial patch favoring the distribution of the first two branches of the trigeminal nerve. Incidence is highest in Asian and Black populations, however, the overwhelming majority of studies are limited to diagnosis and treatment in Asian patients. We herein present 10 Black patients with Fitzpatrick skin types (FST) V and VI who underwent laser treatment for Nevus of Ota. METHODS: We performed a retrospective review of Black patients presenting with Nevus of Ota. Race was self-designated by all patients and documented in the medical record at the time of initial consultation. Primary outcomes were based on improvement using before and after photographs which were graded by three independent board-certified dermatologists using a 5-point visual analog scale. RESULTS: Ten FST V or VI patients with an age range of 9 months to 45 years were treated for Nevus of Ota. All patients were treated with the 1064 nm Q-switched neodymium doped yttrium aluminum garnet (QS Nd:YAG) and on average received 4.7 treatments at 2-10 month intervals. Fluence ranged from 1.8 to 2.3 J/cm2 , and total pulse count ranged from 510.9 to 776.6. 2/10 patients were additionally treated with 1550 nm nonablative fractional resurfacing (NAFR), and 1/10 patients underwent combination therapy with both NAFR and 1064 nm picosecond laser therapy. Overall, patients saw a mean improvement of 51%-75% at follow-up 5-254 weeks (mean 51.5 weeks) after treatment. Three patients experienced mild guttate hypopigmentation in treated areas. No other long-term adverse events were encountered. CONCLUSION: 1064 nm QS Nd:YAG laser therapy is a safe and efficacious treatment for Nevus of Ota in patients with FST V and VI. When patient improvement plateaus, combining therapy with 1550 nm NAFR or transitioning to 1064 nm picosecond laser may be of benefit. Patients should be counseled on the risk of guttate hypopigmentation. This is the largest case series to date of Black patients with Nevus of Ota, highlighting the need for further investigation to determine optimal device settings and treatment parameters for this population.

Combination 1550 nm non-ablative fractional resurfacing and laser hair removal for treatment of Becker's nevi in skin types III-VI.

OBJECTIVES: Becker's nevus is a cosmetically bothersome benign hamartoma typically associated with basal layer hyperpigmentation and hypertrichosis. We herein present the largest case series characterizing treatment parameters and clinical outcomes of combined 1550 nm non-ablative fractional resurfacing and laser hair removal (long-pulsed neodymium-doped yttrium aluminum garnet or alexandrite) in the treatment of Becker's nevus. This is also the largest case series of laser treatment of Becker's nevus in Fitzpatrick skin types V and VI. METHODS: We performed a retrospective review of patients treated between 2016 and 2021. Clinical photographs were graded by three independent physicians using a 5-point visual analog scale. RESULTS: Twelve patients (mean age: 24.8 years, Fitzpatrick skin types III-VI) were treated for Becker's nevus on the face (4) or the trunk and/or extremities (8). Four patients were Fitzpatrick skin types V or VI. On average, patients received 5.3 treatments in 1-4-month intervals. Ten of the 12 patients had concomitant laser hair removal preceding same-day non-ablative fractional resurfacing (n = 7 with long-pulsed 1064 nm neodymium-doped yttrium aluminum garnet and n = 3 with long-pulsed 755 nm alexandrite). The number of treatments with each modality was determined by patient satisfaction with improvement in hyperpigmentation and hypertrichosis. At follow-up, which ranged from 6 to 40 weeks (mean 10.5 weeks), patients were given a mean improvement score of 51%-75%. No long-term adverse events were encountered in either group. Limitations include a small sample size and a lack of long-term follow-up. CONCLUSION: Combination 1550 nm non-ablative fractional resurfacing and laser hair removal is safe and efficacious in the cosmetic reduction of hyperpigmentation and hypertrichosis associated with Becker's nevus, including those with Fitzpatrick skin types V and VI.

Seasonal influenza vaccination during a pandemic.

In the Northern Hemisphere, the persistence or reemergence of coronavirus circulation into the 2020-2021 influenza season threatens to overwhelm health-care resources and systems and increase mortality and morbidity. Data from Australia show that stay-at-home policies have reduced both influenza and coronavirus cases early in the season, thus "flattening the curve." However, influenza vaccination is critical to ensure the reduction in co-infection. Several policies, such as vaccination strategies to accommodate physical distancing measures, change population recommendations, and timing and location of vaccination have been implemented to increase influenza vaccine uptake during the pandemic. This commentary explores those policies.

Cost-effectiveness of introducing an MF59-adjuvanted trivalent influenza vaccine for older adults in Argentina.

INTRODUCTION: Influenza surveillance in Argentina reported influenza-like illness at a rate of 3500/100,000, a hospitalization rate of 15.5/100,000, and a death rate of 0.32/100,000 annually in adults aged over 65 years. The high burden of disease may be due to a combination of immunosenescence and the suboptimal clinical effectiveness of conventional, non-adjuvanted influenza vaccines in this age group. There is a clinical need for more effective influenza vaccines in this population. This study evaluated the cost-effectiveness of an MF59®-adjuvanted trivalent influenza vaccine (aTIV) in adults aged over 65 years in Argentina compared with the non-adjuvanted trivalent influenza vaccine (TIV) used under the current national vaccination policy. METHODS: A decision tree cost-effectiveness model was developed to estimate the cost-effectiveness of switching from TIV to aTIV in Argentinian older adults. The model compared cost and health benefits of vaccination in one influenza season from the payer perspective. The main predictions included survival, quality-adjusted survival, and costs. Model inputs were sourced from Argentina or internationally where local data was considered inaccurate. Vaccine efficacy assumptions were extracted from recently published, peer-reviewed scientific literature. RESULTS: Switching from TIV to aTIV would result in 170 deaths averted and 1310 incremental quality-adjusted life years (QALYs) gained. The incremental cost-effectiveness ratio per QALY was US $2660.59 from the payer perspective. In all sensitivity analyses, aTIV remained highly cost-effective. The probabilistic sensitivity analyses showed a 95% CI per QALY of US $113.74-7721.67. CONCLUSION: Introducing an adjuvanted influenza vaccine in Argentina is potentially beneficial and cost-effective relative to the currently-used TIV through the reduction of disease burden and utilization of healthcare resources.

Treatment of Erythematotelangiectatic Rosacea With Pulsed-Dye Laser and Oxymetazoline 1.0% Cream: A Retrospective Study.

BACKGROUND AND OBJECTIVES: Pulsed-dye laser (PDL) and oxymetazoline 1.0% cream are each used for the treatment of erythematotelangiectatic (ET) rosacea. PDL targets oxyhemoglobin and can reduce facial erythema and telangiectasias. Oxymetazoline 1.0% cream is an α adrenergic agonist, which has shown to reduce facial erythema. The aim of this study was to determine the degree of erythema improvement and telangiectasia clearance after combination treatment with PDL plus oxymetazoline 1.0% cream. STUDY DESIGN/MATERIALS AND METHODS: This retrospective study was conducted at two sites. Pre- and post-treatment cross-polarized images from subjects on combination treatment with PDL and oxymetazoline 1.0% cream were graded by a board-certified dermatologist at each practice. Blinded images were analyzed using the Clinical Erythema Assessment (CEA) Scale (0 = clear and 4 = severe). Unblinded images were analyzed using the five-point Telangiectasia Scale to determine the degree of improvement post-treatment compared with baseline (1 = <5% clearance and 5 = 75-100% clearance). RESULTS: Thirty-one subjects (20 females, 11 males) of age 51 ± 13 years (mean ± standard deviation) were included in the study after an average of 4 months (range: 1-13) of daily oxymetazoline 1.0% cream and two (range: 1-4) PDL treatments. At baseline, 87% of subjects had CEA Grade 2 (mild erythema) or higher. For erythema, 55% of subjects improved by at least one CEA grade and 13% achieved two grades of improvement post-treatment. For telangiectasias, 90% of subjects achieved at least a two-point clearance (5-25%), 62% at least a three-point clearance (25-50%), and 41% at least a four-point clearance (50-75%) post-treatment. Compared with subjects with baseline CEA Grade 1-2 (almost clear to mild erythema), significantly more subjects with baseline CEA Grade 3-4 (moderate to severe erythema) achieved at least one CEA grade of improvement (P = 0.021) and two grades of CEA improvement (P = 0.041). A higher percentage of baseline CEA Grade 3-4 subjects achieved at least a two-point clearance in telangiectasias (P = 0.055). CONCLUSIONS: Combination treatment with PDL and daily oxymetazoline 1.0% cream can safely and effectively reduce erythema and telangiectasias. Limitations include the retrospective design of the study, small sample size, and lack of a control group. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Impact of Clinical Specialty Setting and Geographic Regions on Disease Management in Patients with Psoriatic Arthritis in the United States: A Multicenter Observational Study.

BACKGROUND: Information on the factors that influence treatment management decisions for psoriatic arthritis (PsA) is limited. OBJECTIVE: Our objective was to evaluate the impact of clinical specialty setting and geographic region on the management of patients with PsA in the USA. METHODS: LOOP was a multicenter, cross-sectional, observational study conducted across 44 sites in the USA. Patients were aged ≥ 18 years with a suspected or established diagnosis of PsA and were routinely visiting a rheumatologist or dermatologist. All patients enrolled in the study were assessed by both a rheumatologist and a dermatologist. Primary outcomes were the times from symptom onset to PsA diagnosis; PsA diagnosis to first conventional synthetic disease-modifying antirheumatic drug (csDMARD); PsA diagnosis to first biologic DMARD (bDMARD); and first csDMARD to first bDMARD. RESULTS: Of 681 patients enrolled in the study, 513 had a confirmed diagnosis of PsA and were included in this analysis. More patients were recruited by rheumatologists (71.3%) than by dermatologists (28.7%). The median time from symptom onset to diagnosis of PsA was significantly shorter for patients enrolled by rheumatologists than for those enrolled by dermatologists (1.0 vs. 2.6 years; p < 0.001). Disease activity and burden were generally similar across enrolling specialties. However, patients in western areas of the USA had less severe disease than those in central or eastern areas, including measures of joint involvement, enthesitis, and dactylitis. CONCLUSIONS: There was a substantial delay in the time from symptom onset to diagnosis in this study population, and this was significantly longer for patients enrolled in the dermatology versus the rheumatology setting. This supports the need for collaboration across specialties to ensure faster recognition and treatment of PsA.

Primary and metastatic malignant tumors of the scalp: an update.

In recent years there have been a number of interesting advances in several topics relating to the diagnosis and treatment of cutaneous lesions with particular applicability to primary and metastatic malignancies of the scalp. In this article we provide a general update of advances in this field, and cover the more salient points relating to a variety of malignant tumors that have been reported to appear on the scalp as primary or metastatic lesions. A search and review of the literature on PubMed was made to identify and discuss relevant points relating to diagnosis and treatment of primary and metastatic tumors of the scalp. We describe the anatomy of the scalp, epidemiology of scalp tumors, theories of field cancerization and field therapy, photodynamic therapy, excisional surgical techniques and reconstruction, lymphoscintigraphy, chemoprevention, as well as details relating to atypical fibroxanthoma, Brooke-Spiegler syndrome, nevus sebaceus, cutaneous lymphoma, and metastatic disease. There is a very broad differential diagnosis for scalp nodules, which includes many different benign and malignant diseases, and treatment should be tailored accordingly. Given the potential for poor prognosis with some of the more aggressive malignancies that can be found in this anatomic area, the importance of a thorough physical examination cannot be emphasized enough, and early detection is critical to provide patients with the best chance for a favorable outcome.

Total skin electron beam and non-myeloablative allogeneic hematopoietic stem-cell transplantation in advanced mycosis fungoides and Sezary syndrome.

PURPOSE: Transformed mycosis fungoides (MF) and Sézary syndrome (SS) are currently incurable. We studied the safety and efficacy of total skin electron beam with allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with cutaneous T-cell lymphoma (CTCL). PATIENTS AND METHODS: Nineteen patients with advanced CTCL (median age, 50 years; four prior therapies) underwent total skin electron beam radiation followed by allogeneic HSCT between July 2001 and July 2008. Sixteen patients were conditioned with fludarabine (125 mg/m(2)) and melphalan (140 mg/m(2)) plus thymoglobulin (for mismatched donors). Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus/mini methotrexate. RESULTS: Eighteen patients experienced engraftment, and one died as a result of sepsis on day 16. Median time to recovery of absolute neutrophil count (ANC) was 12 days. Fifteen achieved full donor chimerism, 12 had acute GVHD, and 12 were treated for chronic GVHD. The overall intent-to-treat response was 68%, and the complete response rate was 58%. Four of six patients died in complete remission as a result of bacterial sepsis (n = 2), chronic GVHD and fungal infection (n = 1), or lung cancer (n = 1); only two died as a result of progressive disease. Eight experienced relapse in skin; five regained complete response with reduced immunosuppression or donor lymphocyte infusions. Eleven of 13 are currently in complete remissions, with median follow-up of 19 months (range, 1.3 to 8.3 years). Median overall survival has not been reached. CONCLUSION: Total skin electron beam followed by allogeneic stem-cell transplantation merits additional evaluation for a selected group of patients with refractory, advanced, cutaneous T-cell lymphoma with evidence for graft-versus-tumor effect.

Identification of interleukin-22 in gadoids and examination of its expression level in vaccinated fish.

This paper reports the cloning and sequencing of interleukin (IL)-22 in two gadoid fish, cod (Gadus morhua) and haddock (Melanogrammus aeglefinus). The complete transcript of this gene was 1002 and 1154 bp respectively, of which 492 bp was the open reading frame (ORF) in both genes. High amino acid identity (88.3%) was found between these genes but was less than 50% aa identity to other known genes. The gene organisation of haddock IL-22 consisted of five exons and four introns, as with other IL-10 family members. Expression studies showed that IL-22 is constitutively expressed in gill, with low level expression also observed in gut, gonad and head kidney. In a vaccination experiment, haddock were injected intraperitoneally with formalin-killed Vibrio anguillarum or with PBS, and 2 months later challenged by immersion in 10(7)cfu/ml V. anguillarum for 30 min. Head kidney and gill samples were collected prior to challenge and 24, 48 and 72 h post-challenge (hpc) for Real-time PCR analysis of IL-22 expression. No significant changes in IL-22 expression were observed in head kidney tissue but vaccinated fish showed a significantly increased expression of IL-22 24 hpc in gill and no mortalities were seen in these fish. In contrast, control fish, which started to succumb to the disease from 72 hpc, showed no significant increase in gill expression after challenge.

Induction of T-cell responses against cutaneous T-cell lymphomas ex vivo by autologous dendritic cells transfected with amplified tumor mRNA.

Sézary syndrome (SzS), the leukemic variant of cutaneous T-cell lymphomas, is incurable. Dendritic cells (DCs) transfected with tumor mRNA can stimulate antitumor immunity in certain cancer patients. In this study, we determined whether mRNAs from Sézary cells could be used for loading DCs and stimulating antitumor immunity. Autologous DCs were generated from monocytes of the peripheral blood from 10 patients with SzS. Total RNA was extracted from Sézary cells and amplified by T7 in vitro transcription. The induction of antitumor IFN-gamma and granzyme B (GrB)-producing cytotoxic T lymphocytes (CTL) by RNA-transfected DCs was determined by ELISPOT assays. We found that IFN-gamma was required for IL-12p70 production by monocyte-derived DCs from SzS. The oncogenic transcription factor Twist and the tyrosine kinase receptor EphA4 were expressed in total RNA from Sézary cells and the paired amplified mRNAs. RNA-transfected DCs induced antitumor IFN-gamma-producing CTLs in 7 of 10 subjects and GrB-producing CTLs in 6 of 9 subjects. Both CD3+CD8+ T cells and CD4+CD25+ T cells were expanded without induction of regulatory T cells. These data support the concept of using tumor mRNA for a vaccine strategy that requires small amounts of tumor cells without need for specific antigens in patients with SzS.

Primary cutaneous follicle center lymphoma associated with alopecia areata.

We report a patient who presented simultaneously with primary cutaneous follicle center lymphoma (PCFCL) of the face and scalp and alopecia areata of the scalp and beard bearing a clonal T-cell receptor gene rearrangement. To our knowledge, alopecia areata has not been previously reported in association with PCFCL. Both lesions regressed with topical imiquimod and systemic steroids, which suggests an inter-relationship in this case between the clonal B-cell and T-cell populations in driving outgrowth of these lesions.

Nephrogenic systemic fibrosis: relationship to gadolinium and response to photopheresis.

BACKGROUND: Nephrogenic systemic fibrosis (NSF), previously known as nephrogenic fibrosing dermopathy, is an idiopathic condition seen in patients with renal disease that is characterized by cutaneous sclerosis that can often result in contractures, pain, and functional disability as well as systemic complications. Recent reports have suggested a possible link with exposure to gadolinium, a commonly used radiocontrast agent. No current therapy has clearly demonstrated efficacy for NSF, although case reports suggest that extracorporeal photopheresis (ECP) may be of benefit. The purpose of this study was to explore the plausibility of a gadolinium linkage with NSF as well as to assess the efficacy of ECP in the treatment of a cohort of patients with NSF. OBSERVATIONS: We report our experience with 8 consecutive patients with NSF seen at the Stanford Medical Center, Palo Alta, California, from 2004 to 2006. Of the 8 patients, 6 had a history of arterial or venous thrombotic disease and 7 had a documented exposure to gadolinium within 1 week to several months prior to the onset of NSF. Specifically, all patients were exposed to gadodiamide. We treated 5 of the patients with ECP. After a mean number of 34 treatment sessions over a mean of 8.5 months, 3 patients experienced a mild improvement in skin tightening, range of motion, and/or functional capacity. CONCLUSIONS: Our data support the hypothesis that exposure to gadolinium, perhaps specifically gadodiamide, plays a role in the pathogenesis of NSF. Larger epidemiologic studies will be needed to confirm this association. In addition, our experience suggests that, if used for extended periods, ECP might have some mild benefit for patients with NSF. Larger, randomized, placebo-controlled trials of ECP should be performed to more specifically assess the benefit of ECP in the treatment of NSF.

The mechanical behavior of activated skeletal muscle during stretch: effects of muscle unloading and MyHC isoform shifts.

The response of activated skeletal muscle to a ramp stretch is complex. Force rises rapidly above the isometric plateau during the initial phase of stretch. However, after a strain of approximately 1-2%, force yields and continues to rise but with a slower slope. The resistance to stretch during the initial phase can be characterized by the stiffness of the muscle and/or the preyield modulus (E(pre)). Similarly, a measure of modulus also can be used to characterize the postyield modulus response (E(post)). This study examined the effects of muscle atrophy and altered myosin heavy chain (MyHC) isoform composition on both E(pre) and E(post). Female Sprague-Dawley rats were assigned to 1) control group, 2) a hypothyroid group, 3) a hyperthyroid group, 4) a hindlimb suspension group, and 5) a hindlimb suspension + hyperthyroid group. These interventions were used either to alter the MyHC isoform composition of the muscle or to induce atrophy. Soleus muscles were stretched at strain rates that ranged from approximately 0.15 to 1.25 muscle length/s. The findings of this study demonstrate that 4 wk of hindlimb suspension can produce a large (i.e., 40-60%) reduction in E(pre). Hindlimb suspension did not produce a proportional change in E(post). Analyses of the E(pre)-strain rate relationship demonstrated that there was little dependence on MyHC isoform composition. In summary, the disproportionate decrease in E(pre) of atrophied muscle has important implications with respect to issues related to joint stability, especially under dynamic conditions and conditions where the static joint stabilizers (i.e., ligaments) have been compromised by injury.