Use of excimer laser for morphea

Background and Objectives: Morphea, also known as localized scleroderma, is a sclerotic inflammatory disorder that primarily affects the skin but has the potential to involve fascia, muscle and bones. With no cure for this disfiguring disease, therapeutic modalities including topical regiments, immunosuppressive agents, antimalarial medications, and phototherapy are used to manage the symptoms and progression. While many treatments options are available, they vary in efficacy. Methods: We present a case of a 28-year-old woman with active sclerotic plaques distributed along her neck, left flank. She had previously failed therapy with topical steroids and methotrexate, and was started on hydroxychloroquine 400 mg daily and calcipotriene/betamethasone ointment 0.005% BID. Since she was still having active lesions, she was referred to our clinic for consultation regarding excimer laser therapy. We used excimer laser therapy at 260 mJ twice a week, supplementing the hydroxychloroquine and calcipotriene/betamethasone ointment. Results and Conclusion: Within two months of therapy, no new lesions had occurred and current lesions showed no active inflammation. To our knowledge, this is the first description of excimer laser used for the treatment of morphea

Review of Applications of Microneedling in Dermatology.

Microneedling (MN) is a novel therapeutic modality in dermatology. Through physical trauma from needle penetration, MN induces a wound healing cascade with minimal damage to the epidermis. This allows for enhancement in the absorption of mainstay topical therapies across the thick stratum corneum. MN has become increasingly utilized over the last several years as it is a relatively simple procedure that is cost-effective, well tolerated, and offers both cosmetic and therapeutic benefits. The ability to treat localized areas of disease has led to numerous studies gauging its potential in focal diseases of inflammation, dyschromia, and photodamage. This review discusses the principles and evidence behind the expanding applications of MN. It has shown promising results as an adjuvant therapy for enhanced drug delivery in the treatment of atrophic scars, alopecia, actinic keratoses, and disorders of pigmentation such as melasma. The efficacy in treatment of vitiligo remains limited. Overall, the procedure has few adverse sequelae compared to other therapies, is highly efficacious, and is a viable resurfacing option for skin of color. Future research is needed to determine the frequency, interval, and specific device settings that foster optimal results. Additionally, large controlled trials are needed to shed light on the utility of MN as an evidence-based regimen for the treatment of various dermatologic conditions

The site and stoichiometry of the N-phenylmaleimide reaction with myosin when weakly-binding crossbridges are formed in skinned rabbit psoas fibers

AbstractTreatment of relaxed skinned rabbit psoas muscle fibers with 0.1 mM N-phenylmaleimide (NPM) for 1 h locks all of the crossbridges in a weakly-binding state resembling that of the myosin ATP crossbridge. Under these conditions, NPM reacts mainly with myosin heavy chain (Barnett et al. (1992) Biophys. J. 61, 358–367). Here the specific sites for that reaction are explored. Small bundles of rabbit psoas muscle fibers were treated with Triton X-100 to make the fiber sarcolemmas permeable. The bundles were treated with 0.1 mM [14C]NPM for 1 h, and homogenized for SDS-PAGE. 43 ± 2.2% of the muscle fiber protein ran in the myosin heavy chain band, the same as for untreated fibers. An alkylating stoichiometry of 2.2 ± 0.33 moles NPM per mole myosin heavy chain was determined. Exhaustive trypsin digestion followed by two-dimensional thin-layer chromatography and reverse-phase HPLC revealed two major sites on myosin heavy chain for NPM binding. The sites contained about the same amount of linked NPM, suggesting that the reaction stoichiometry of each site under the conditions studied is approx. 1 mol NPM/mol myosin heavy chain. Comparison of the labeled tryptic peptides with NPM-reacted synthetic SH1 and SH2 tryptic peptides and analysis of the treated fiber bundles' ATPase activity suggested that the sites for NPM reaction on myosin heavy chain when it locks crossbridges in a weakly-binding state are Cys-697 (SH2) and Cys-707 (SH1)

Biclonal gammopathy in a patient taking efalizumab for the treatment of psoriasis

We report a patient who developed biclonal gammopathy of undetermined significance during treatment withefalizumab for psoriasis. This plasma cell disorder was found during the evaluation of the patient’s complaint of mild lower extremity paresthesia. The gammopathy spontaneously remitted following cessation of therapy and has not recurred to date. Given the increasing use and development of biological agents for the treatment of psoriasis and other disorders, this finding and the mechanisms by which it may have occurred is of clinical significance

Profile of dupilumab and its potential in the treatment of inadequately controlled moderate-to-severe atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disorder that manifests as eczematous lesions, often associated with allergic rhinitis and asthma. Historically, moderate-to-severe disease has been managed with systemic immunosuppression, such as oral corticosteroids, which result in relapse and limiting side effects. Due to recent advancements in the identification of interleukin (IL)-4 and IL-13 as key mediators in AD, new biological agents have been developed for treatment. Dupilumab is a recently approved monoclonal antibody that targets the alpha subunit of the IL-4 receptor and, thus, downregulates activity of IL-4 and IL-13. This review discusses the profile of dupilumab and its potential for efficacy and safety in treating moderate-to-severe AD by reviewing data from Phase I-III clinical trials. Results suggest that dupilumab shows great therapeutic promise for AD. Further studies investigating extended use of dupilumab and dupilumab in comparison to other agents are needed to establish long-term efficacy and safety

Trends in silicosis prevalence and the healthy worker effect among gold miners in South Africa: a prevalence study with follow up of employment status.

BACKGROUND: Given the intimate association between silicosis and tuberculosis, understanding the epidemiology of the South African gold mining industry silicosis epidemic is essential to current initiatives to control both silicosis and tuberculosis in this population, one of the most heavily affected globally. The study's objectives were to compare the prevalence of silicosis among working black gold miners in South Africa during 2004-2009 to that of previous studies, including autopsy series, and to analyse the influence of silicosis and/or tuberculosis on exiting employment. METHODS: Routine chest radiographs from a cohort of gold miners were read for silicosis by an experienced reader (I), and a subset re-read by a B-trained reader (II). Two methods of presenting the readings were used. Additionally, with baseline status of silicosis and previous or active tuberculosis as predictors, survival analysis examined the probability of exiting the workforce for any reason during 2006-2011. RESULTS: Reader I read 11 557 chest radiographs and reader II re-read 841. Overall, silicosis prevalence (ILO ≥ 1/0: 5.7 and 6.2% depending on reader method) was similar to the age adjusted prevalence found in a large study in 1984 (5.0%). When comparison was restricted to a single mine shaft previously studied in 2000, a decline in prevalence (ILO ≥ 1/1) was suggested for one of the reading methods (duration adjusted 20.5% vs. 13.0% in the current study). These findings are discordant with a long-term rising autopsy prevalence of silicosis over this period. Overall, relative to miners with neither disease, the adjusted hazard ratio for exiting employment during the follow-up period was 1.54 for baseline silicosis [95% confidence interval (CI) 1.17, 2.04], 1.71 for tuberculosis (95% CI 1.51, 1.94) and 1.53 for combined disease (95% CI 1.20, 1.96). CONCLUSIONS: This study found, a) there was no significant decline in overall silicosis prevalence among working black miners in the South African gold mining industry between 1984 and 2004-2009, and b) a possible decline at one mine shaft more recently. In the absence of evidence of declining respirable silica concentrations between the 1980s and 2000s, the trends found are plausibly due to a healthy worker survivor effect, which may be accelerating

Predictors of silicosis and variation in prevalence across mines among employed gold miners in South Africa

Background The stated intention to eliminate silicosis from the South African goldmining industry as well as current programmes to find and compensate ex-miners with silicosis require an understanding of variation in silicosis prevalence across the industry. We aimed to identify the predictors of radiological silicosis in a large sample of working miners across gold mines in South Africa. Methods Routine surveillance chest radiographs were collected from 15 goldmine “clusters” in a baseline survey undertaken in preparation for a separate tuberculosis isoniazid prophylaxis trial. All images were read for silicosis by a health professional experienced in using the International Labour Organisation (ILO) classification. Profusion thresholds of > 1/0 and > 1/1 were used. Demographic and occupational information was obtained by questionnaire. Predictors of silicosis were examined in a multivariable logistic regression model, including age, gender, racial ascription, country of origin, years since starting mine employment, mine shaft, skill category, underground work status and tuberculosis. Results The crude silicosis prevalence at ILO > 1/1 was 3.8% [95% confidence interval (CI) 3.5–4.1%]. The range across mine shafts was 0.8–6.9%. After adjustment for covariates, the interquartile range across shafts was reduced from 2.4 to 1.2%. Black miners [adjusted odds ratio (aOR) 2.8; 95% CI 1.1–7.2] and miners in full-time underground work (aOR 2.1; 95% CI 1.3–3.4) had substantially elevated odds of silicosis, while workers from Mozambique had lower odds (aOR 0.54; 95% CI 0.38–0.77). Silicosis odds rose sharply with both age and years since starting in the industry (p for linear trend  15 years since first exposure and 2.2% < 10 years. Conclusions In surveillance of silicosis in working gold miners time since first exposure remains a powerful predictor. Age appears to be an independent predictor, while the detection of radiological silicosis in short-service miners requires attention. Public risk reporting by mines should include factors bearing on silicosis prevalence, specifically dust concentrations, with independent verification. Studies of silicosis and tuberculosis in ex-miners are needed, supported by an accessible electronic database of the relevant medical and dust exposure records of all gold miners

When is a GIST not a GIST? A case report of synchronous metastatic gastrointestinal stromal tumor and fibromatosis

<p>Abstract</p> <p>Background</p> <p>A number of non-malignant diseases that share similar morphological features as gastrointestinal stromal tumor (GIST) have been reported. Co-existence of GIST with these other diseases is rarely recognized or reported.</p> <p>Case presentation</p> <p>We report a case of a 62 year-old man with long-term stable control of metastatic GIST with systemic therapy, presented with an apparent intra-abdominal progression but not supported by imaging with positron emission tomography. Subsequent resection of the intra-abdominal tumor identified a non-malignant fibroid.</p> <p>Conclusion</p> <p>Differentiating localized progression of GIST from other diseases has important prognostic and therapeutic implications. The potential for co-existence of non-malignant soft tissue neoplasm should always be considered.</p

Severity of Psoriasis Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil Activation in a Prospective Observational Study.

This is the author accepted manuscript. The final version is available from the American Heart Association via http://dx.doi.org/10.1161/ATVBAHA.115.306460OBJECTIVE: To understand whether directly measured psoriasis severity is associated with vascular inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography computed tomography. APPROACH: In-depth cardiovascular and metabolic phenotyping was performed in adult psoriasis patients (n=60) and controls (n=20). Psoriasis severity was measured using psoriasis area severity index. Vascular inflammation was measured using average aortic target-to-background ratio using (18)F-fluorodeoxyglucose positron emission tomography computed tomography. RESULTS: Both the psoriasis patients (28 men and 32 women, mean age 47 years) and controls (13 men and 7 women, mean age 41 years) were young with low cardiovascular risk. Psoriasis area severity index scores (median 5.4; interquartile range 2.8-8.3) were consistent with mild-to-moderate skin disease severity. Increasing psoriasis area severity index score was associated with an increase in aortic target-to-background ratio (β=0.41, P=0.001), an association that changed little after adjustment for age, sex, and Framingham risk score. We observed evidence of increased neutrophil frequency (mean psoriasis, 3.7±1.2 versus 2.9±1.2; P=0.02) and activation by lower neutrophil surface CD16 and CD62L in blood. Serum levels of S100A8/A9 (745.1±53.3 versus 195.4±157.8 ng/mL; P<0.01) and neutrophil elastase-1 (43.0±2.4 versus 30.8±6.7 ng/mL; P<0.001) were elevated in psoriasis. Finally, S100A8/A9 protein was related to both psoriasis skin disease severity (β=0.53; P=0.02) and vascular inflammation (β=0.48; P=0.02). CONCLUSIONS: Psoriasis severity is associated with vascular inflammation beyond cardiovascular risk factors. Psoriasis increased neutrophil activation and neutrophil markers, and S100A8/A9 was related to both skin disease severity and vascular inflammation.JMT is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z) and the NIHR Cambridge Biomedical Research Centre. JHFR is part-supported by the HEFCE, the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trus

Prevalence of Concurrent Functional Vision and Hearing Impairment and Association With Dementia in Community-Dwelling Medicare Beneficiaries.

IMPORTANCE: Impairments in vision or hearing are common and have been independently linked to higher risk of dementia in older adults. There is a limited understanding of the prevalence of concurrent functional vision and hearing impairment (dual sensory impairment) and its contribution to dementia risk. OBJECTIVE: To examine the age-specific prevalence of functional dual sensory impairment among older adults, and to investigate the cross-sectional and 7-year longitudinal associations between functional dual sensory impairment and dementia. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of 7562 older adults used data from the US National Health and Aging Trends Study (NHATS), a nationally representative cohort study of community-dwelling, Medicare beneficiaries aged 65 years and older in the US. Participants in the study with complete data on hearing, vision, and dementia were included in analysis. Data were collected between 2011 and 2018, and between March 2018 and May 2020. EXPOSURES: Self-reported functional sensory impairments (ie, no sensory impairment, functional vision impairment only, functional hearing impairment only, and functional dual sensory impairment). MAIN OUTCOMES AND MEASURES: Age-specific prevalence of functional sensory impairments was calculated. Generalized linear regression with a complementary log-log link and a discrete time proportional hazards model with a complementary log-log link were used to assess the cross-sectional and 7-year longitudinal hazard of dementia. RESULTS: Of 7562 participants, 3073 (40.7%) were ages 80 years or older and 4411 (58.3%) were women. Overall, 5.4% (95% CI, 4.7%-6.1%) of participants reported functional vision impairment only, 18.9% (95% CI, 18.9%-17.8%) reported functional hearing impairment only, and 3.1% (95% CI, 2.7%-3.5%) reported functional dual sensory impairment (prevalence estimates are weighted). Participants reporting sensory impairments were older (no impairment: age ≥90 years, 2.12% [95% CI, 1.79%-2.46%] vs functional dual sensory impairment: age ≥90 years, 20.06% [95% CI, 16.02%-24.10%]), had lower education (no impairment: <high school, 19.05% [95% CI, 17.27%-20.83%] vs functional dual sensory impairment: <high school, 46.15% [95% CI, 38.38%-53.92%]), and greater disease burden (eg, heart disease: no impairment, 15.30% [95% CI, 14.04%-16.55%] vs functional dual sensory impairment, 25.49% [95% CI, 19.96%-31.02%]). Compared with no impairment, functional vision impairment (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.57-2.28), functional hearing impairment (aHR, 1.14; 95% CI, 1.00-1.31), and functional dual sensory impairment (aHR, 2.00; 95% CI, 1.57-2.53) were associated with a higher cross-sectional hazard of dementia. Over 7 years, functional vision impairment (aHR, 1.40; 95% CI, 1.12-1.74), functional hearing impairment (aHR, 1.09; 95% CI, 0.95-1.24), and functional dual sensory impairment (aHR, 1.50; 95% CI, 1.12-2.02) were associated with a higher hazard of incident dementia compared with no impairment. CONCLUSIONS AND RELEVANCE: In this cohort study of US Medicare beneficiaries, dual sensory impairment was prevalent in older adults and associated with increased risk of dementia. These findings suggest that sensory rehabilitative interventions for multiple impairments may be an additional resource in efforts to reduce dementia risk