Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia (FM) is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS).</p> <p>Results</p> <p>In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief.</p> <p>Conclusions</p> <p>These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.</p

Baseline Demographics, Comorbidities, Treatment Patterns and Burden of Atopic Dermatitis in Adults and Adolescents from the GLOBOSTAD Long-Term Observational Study

Introduction - Insights into real-world treatment of atopic dermatitis (AD) are relevant to clinical decision making. The aim of this analysis was to characterize patients who receive dupilumab for AD in a real-world setting. Methods - The GLOBOSTAD registry is an ongoing, longitudinal, prospective, observational study of patients with AD who receive dupilumab according to country-specific prescribing information. We report baseline characteristics, comorbidities and treatment patterns for patients enrolled from July 11, 2019 to March 31, 2022. Analyses are descriptive; no formal statistical comparisons were performed. Results - Nine hundred fifty-two adults and adolescents were enrolled in GLOBOSTAD. Patients had a high disease burden before starting dupilumab: (mean [standard deviation]) percent body surface area affected (44.8 [24.42]), Eczema Area and Severity Index total score (24.8 [12.95]), SCORing Atopic Dermatitis total score (60.5 [16.34]), Patient-Oriented Eczema Measure total score (19.7 [6.37]) and Dermatology Life Quality Index total score (13.7 [7.02]). Overall, 741 (77.8%) patients reported ≥ 1 type 2 inflammatory comorbidities, most frequently allergic rhinitis (492 [51.7%]), asthma (323 [33.9%]), food allergy (294 [30.9%]) or another allergy (274 [28.8%]). In the previous 12 months, 310 (32.6%) patients had received systemic non-steroidal immunosuppressants and 169 (17.8%) systemic corticosteroids; 449 (47.2%) had received topical corticosteroids, most commonly potent topical corticosteroids; 141 (14.8%) had received topical calcineurin inhibitors and 32 (3.4%) ultraviolet therapy. Most (713 [74.9%]) patients started dupilumab because of prior treatment failure. Conclusion - Patients enrolled in GLOBOSTAD demonstrated considerable multidimensional burden of disease across AD signs, symptoms and quality of life despite previous use of systemic and non-systemic AD treatments

What causes hidradenitis suppurativa? - 15 years after

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa Research Symposium held March 30?April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote "Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy." (Kurzen et al. What causes hidradenitis suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, there is no doubt that the desired renaissance of solid basic HS research is progressing with rapid steps and that HS has developed deep roots among inflammatory diseases in Dermatology and beyond, recognized as ?the only inflammatory skin disease than can be healed?. This anniversary article of 43 research-performing authors from all around the globe in the official journal of the European Hidradenitis Suppurativa Foundation e.V. (EHSF e.V.) and the Hidradenitis Suppurativa Foundation, Inc (HSF USA) summarizes the evidence of the intense HS clinical and experimental research during the last 15 years in all aspects of the disease and provides information of the developments to come in the near future

Aging Skin: Nourishing from the Inside Out, Effects of Good Versus Poor Nitrogen Intake on Skin Health and Healing

Skin is the outermost defense organ which protects us from the environment, constituting around 8 % of an adult’s body weight. Healthy skin contains one-eighth of the body’s total proteins. The balance of turnover and synthesis of skin proteins is primarily dependent on the availability of sufficient nitrogen-containing substrates, namely, amino acids, essential for protein metabolism in any other tissue and body organs. The turnover of skin proteins has been shown to be rapid, and the mobilization of amino acids at the expense of skin proteins is relevant in experimental models of protein malnutrition. As a result, alterations in nutritional status should be suspected, diagnosed, and eventually treated for any skin lesions. Protein malnutrition has a dramatic prevalence in patients aged >70 or more, independent of the reason for hospitalization. The quality of nutrition and content of essential amino acids are strictly connected to skin health and integrity of its protein components. Collagen fiber deposition is highly and rapidly influenced by alterations in the essential to nonessential amino acid ratios. The most relevant nutritional factor of skin health is the prevalence of essential amino acids

Carotid ultrasound is useful for the cardiovascular risk stratification in patients with hidradenitis suppurativa

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease which has been associated with an increased risk of adverse cardiovascular (CV) outcomes. Adequate stratification of the CV risk is an issue of major importance in patients with HS. To analyze the usefulness of carotid ultrasound (US) assessment for the CV disease risk stratification compared with a traditional score, the Framingham risk score (FRS), in a series of patients with HS. METHODS: Cross-sectional study of 60 patients with HS without history of CV events, diabetes mellitus or chronic kidney disease. Information on CV risk factors was collected and the FRS was calculated. Thus, the patients were classified into low, intermediate and high-CV disease risk categories based on FRS. Carotid US was performed in all participants, and the presence of atherosclerotic plaques was considered as a marker of high CV risk. RESULTS: HS patients had a mean age of 45.1±10.2 years, and 55% were female. The median FRS was 5.7 (IQR: 3.1-14.7). Twenty-four (40%) of the patients were classified into the low risk group, 28 (46.7%) in the intermediate risk group, and 8 (13.3%) into the FRS-high risk category. Noteworthy, carotid US revealed that about one-third of the patients (17/52; 32.6%) in the FRS-based low and intermediate risk categories had carotid plaques, and, therefore, they were reclassified into a high-risk category. CONCLUSION: CV risk in HS patients may be underestimated by using the FRS. Carotid US may be useful to improve the CV risk stratification of patients with HS.This study was funded through an unrestricted grant provided by AbbVie to MGL. AbbVie has not played any role in study design, data collection and analysis, decision to publish or preparation of the manuscript

What causes hidradenitis suppurativa ?—15 years after

The 14 authors of the first review article on hidradenitis suppurativa (HS) pathogenesis published 2008 in EXPERIMENTAL DERMATOLOGY cumulating from the 1st International Hidradenitis Suppurativa Research Symposium held March 30–April 2, 2006 in Dessau, Germany with 33 participants were prophetic when they wrote “Hopefully, this heralds a welcome new tradition: to get to the molecular heart of HS pathogenesis, which can only be achieved by a renaissance of solid basic HS research, as the key to developing more effective HS therapy.” (Kurzen et al. What causes hidradenitis suppurativa? Exp Dermatol 2008;17:455). Fifteen years later, th

Sentinel lymph node biopsy followed by lymph node dissection for localised primary cutaneous melanoma

Background: Melanoma is the leading cause of skin cancer-associated mortality. The vast majority of newly diagnosed melanomas are confined to the primary cutaneous site. Surgery represents the mainstay of melanoma treatment. Treatment strategies include wide excision of the primary tumour and sentinel lymph node biopsy (SLNB) to assess the status of the regional nodal basin(s). SLNB has become an important component of initial melanoma management providing accurate disease staging. Objectives: To assess the effects and safety of SLNB followed by completion lymph node dissection (CLND) for the treatment of localised primary cutaneous melanoma. Search methods: We searched the following databases up to February 2015: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2015, Issue 1), MEDLINE (from 1946), EMBASE (from 1974), and LILACS ((Latin American and Caribbean Health Science Information database, from 1982). We also searched the following from inception: African Index Medicus, IndMED of India, Index Medicus for the South-East Asia Region, and six trials registers. We checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We searched ISI Web of Science Conference Proceedings from inception to February 2015, and we scanned the abstracts of major dermatology and oncology conference proceedings up to 2015. Selection criteria: Two review authors independently assessed all RCTs comparing SLNB followed by CLND for the treatment of primary localised cutaneous melanoma for inclusion. Primary outcome measures were overall survival and rate of treatment complications and side effects. Data collection and analysis: Two review authors independently extracted and analysed data on survival and recurrence, assessed risk of bias, and collected adverse effect information from included trials. Main results: We identified and included a single eligible trial comparing SLNB with observation which was published in eight different reports (from 2005 to 2014) with 2001 participants. This trial did not report on our first primary outcome of overall survival (which was also the planned primary outcome of this trial). When contacted for this important data, the trial authors stated &quot;there are numerous additional analyses that have yet to be reported for the trial&quot;. We were able however to estimate overall survival from data included in the appendix of the published report and found no evidence of benefit for SLNB for overall survival. The overall survival hazard ratio (HR) using ITT (intention-to-treat) analysis was 0.99 95% confidence interval [CI] 0.82 to 1.19, 1661 participants). The overall survival using ITT for intermediate thickness melanomas was (HR 0.92, 95% CI 0.73 to 1.16) and for thick melanomas it was (HR 1.15, 95% CI 0.82 to 1.61). The study did report on our second primary outcome of rate of treatment complications: short-term surgical morbidity (30 days) in 1735 participants showed no difference between SLNB and observation (risk ratio [RR] 1.11, 955 CI 0.9 to 1.37) for wide excision of the tumour site but favoured observation for complications related to the regional nodal basin (RR 14.36, 95% CI 6.74 to 30.59). Our secondary outcomes of disease-specific and disease-free survival, local recurrence and distant metastases were reported. There were 1347 participants in the intermediate-thickness melanoma group and 314 in the thick melanoma group.The study did not report the actual 10-year melanoma-specific survival rate for all included participants. Instead, melanoma-specific survival rates for each group of participants: intermediate-thickness melanoma (defined as 1.2 to 3.5 mm) and thick melanomas (defined as 3.50 mm or more) was reported. In the intermediate-thickness melanoma group there was no statistically significant difference in disease-specific survival between study groups at 10 years (81.4 ± 1.5% versus 78.3 ± 2.0%, HR 0.84, 95% CI 0.65 to 1.09). In the thick melanoma group, again there was no statistically significant difference in disease-specific survival between study groups at 10 years (58.9.3 ± 4.1% versus 64.4 ± 4.6%, HR 1.12, 95% CI 0.77 to 1.64). Combining these groups there was some heterogeneity (I2 = 34%) but the total HR was not statistically significant (HR 0.92, 95% CI 0.74 to 1.14). The summary estimate for disease-free survival at 10 years favoured SLNB over observation in participants with intermediate-thickness and thick melanomas (HR 0.75, 95% CI 0.63 to 0.89). With regard to the rate of local and regional recurrence as the site of first recurrence, a benefit of SLNB uniformly existed in both groups of participants with intermediate-thickness and thick melanomas (RR 0.56, 95% CI 0.45 to 0.69). This is in contrast with a uniformly unfavourable effect of SLNB with regard to the rate of distant metastases as site of first recurrence, in both groups of participants with intermediate-thickness and thick melanomas (HR 1.33, 95% CI 1.03 to 1.72). Authors&apos; conclusions: We found no evidence of improved overall survival or melanoma-specific survival rates for participants with intermediate or thick melanomas who underwent SLNB compared with observation alone. Disease-free survival and rate of local and regional recurrence favoured SLNB in both groups of participants with intermediate-thickness and thick melanomas but short-term surgical morbidity was higher in the SLNB group, especially with regard to complications in the nodal basin. The evidence for the outcomes of interest in this review is of low quality due to the risk of bias and imprecision of the estimated effects. Further research may have an important impact on our estimate of the effectiveness of SLNB in managing primary localised cutaneous melanoma. Currently this evidence is not sufficient to document a benefit of SLNB when compared to observation in individuals with primary localised cutaneous melanoma. © 2017 The Cochrane Collaboration. Published by John Wiley &amp; Sons, Ltd

Accuracy of dermoscopic criteria for discriminating superficial from other subtypes of basal cell carcinoma

Background The management of basal cell carcinoma (BCC) depends, among other factors, on its histopathologic subtype. Although dermoscopic criteria of BCC have been investigated, the possible role of dermoscopy in predicting the tumor subtype remains unclear. Objectives We sought to assess the diagnostic accuracy of dermoscopic criteria for differentiating superficial BCC (sBCC) from other BCC subtypes. Methods Dermoscopic images of histopathologically confirmed BCCs were retrospectively evaluated for the presence of predefined criteria. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver operating characteristic curves. Results In all, 77 sBCCs and 258 non-sBCCs were included. Maple leaf-like areas, short fine superficial telangiectasia, multiple small erosions, and shiny white-red structureless areas were potent predictors of sBCC, each making its diagnosis over 5-fold more likely. Conversely, the presence of arborizing vessels, blue-gray ovoid nests, and ulceration gave 11-fold, 15-fold, and 3-fold increased possibility for the diagnosis of non-sBCCs, respectively. Based on the results of the multivariate analysis, we propose a diagnostic algorithm that can predict the diagnosis of sBCC with a sensitivity of 81.9% and a specificity of 81.8%. Limitations The retrospective design and the inclusion of only Caucasian patients are limitations. Conclusion Dermoscopy is reliable in differentiating sBCC from other BCC subtypes. © 2013 by the American Academy of Dermatology, Inc