Efficacy of Botulinum Toxin in the Treatment of Cutaneous Flushing: A Systematic Review and Meta-Analysis.

BACKGROUND: Flushing is a common dermatologic complaint and can be resistant to many treatments. As the utility of botulinum toxin continues to expand, recent data suggest that it may also be a therapeutic option for flushing. OBJECTIVE: To evaluate the efficacy of botulinum toxin for the treatment of cutaneous flushing. MATERIALS AND METHODS: A systematic search of Medline, Embase, Cochrane CENTRAL, CINAHL, Scopus, and Web of Science databases was conducted to identify studies evaluating the effect of botulinum toxin on flushing 1 month after treatment. Prespecified outcome measures included a clinical flushing score, dermatology life quality index (DLQI), and erythema index (EI). Meta-analysis was performed to calculate the mean differences in these outcomes before and after treatment at 1-month follow-up. RESULTS: Nine studies (132 patients) were included in the analysis of this study (2 randomized controlled trials and 7 nonrandomized studies). All studies had a low risk of bias (high quality). The most frequent outcome reported was a clinical flushing score, which significantly decreased by 1.25 points overall (95% confidence interval [CI]: -2.47; -0.04) 1 month after treatment with botulinum toxin. Mean DLQI scores decreased (i.e., improved) by 9.02 points (95% CI: -19.81; 1.77) 1 month after botulinum toxin injections. The EI (measured by Mexameter) before and after botulinum toxin was evaluated in 2 studies; however, not enough statistical information was provided to analyze with meta-analytic techniques. CONCLUSION: Based on this meta-analysis, botulinum toxin significantly improves clinical flushing scores 1 month after treatment.

Beyond the Label: Real-World Side Effects Experienced With FDA-Approved Drugs for Non-Melanoma Skin Cancers.

With immunotherapy historically focused on cutaneous melanoma, there has been a new wave of systemic medications available for treating non-melanoma skin cancers including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC). The immune checkpoint inhibitors approved by the FDA target programmed cell death protein 1 (PD-1) and the Hedgehog (Hh) signaling pathway. These medications have expanded treatment options; however, side effects are an important consideration. We used the FDA Adverse Events Reporting System (FAERS) to characterize the most prevalent, real-world side effects experienced by patients on these agents. Muscle spasms (23.45%), alopecia (16.06%), ageusia (12.02%), taste disorder (11.91%), and fatigue (11.67%) were the five most common side effects reported with medications used for BCC treatment. Logistic regression analysis showed males on vismodegib for BCC having greater odds of experiencing muscle spasms (aOR 1.33, P<0.001) and ageusia (aOR 1.34,  P<0.001) versus females, who were more likely to exhibit alopecia (aOR 1.82, P<0.001) and nausea (aOR 1.96, P<0.001). With SCC treatment, the 5 most reported adverse events were fatigue (5.58%), rash (3.59%), asthenia (3.59%), pruritus (3.19%), and pyrexia (2.79%). Patients taking cemiplimab-rwlc for BCC compared to SCC were more likely to experience disease progression (aOR 10.98, P=0.02). With medication labels providing an excessively daunting list of side effects, we characterize practical side effects seen in patients receiving systemic treatments for non-melanoma skin cancers.  J Drugs Dermatol. 2024;23(5):301-305. doi:10.36849/JDD.7968.

The distribution of industry payments among pediatric dermatologists from 2015 to 2021.

BACKGROUND/OBJECTIVES: To understand the landscape of industry payments to pediatric dermatologists to foster transparency and identify potential disparities in funding. METHODS: Using the Centers for Medicare and Medicaid Services (CMS) Open Payments database, a national cross-sectional study was performed examining payments to pediatric dermatologists from 2015 to 2021. RESULTS: Of the 147 pediatric dermatologists who received industry funding, 35 were male and 112 were female. $9 million in payments was amassed, with 10% of pediatric dermatologists accounting for 94% of total industry payments. Consulting was the most common service, with Pfizer Inc., Amgen Inc., and Regeneron Healthcare Solutions Inc. representing the top three companies. Mean payment was $143,836 for males and $35,943 for females (p < .001). Eight female and seven male pediatric dermatologists received payments in the top 10th percentile, with different average payment in this subgroup (females $447,588 vs. males $698,746, p = .03). 11 states did not have a pediatric dermatologist receiving industry payments, while California (19) and Texas (12) had the most. CONCLUSIONS: There are approximately 400 board-certified pediatric dermatologists in the United States and fewer than 40% are receiving monetary compensation from private industry. A fraction of physicians accounted for a majority of total industry payments and industry payments to male pediatric dermatologists were higher despite nearly triple the number of female pediatric dermatologists. With the rise of valuable partnerships between healthcare and industry in modern medicine, the implications of geographic, gender, and financial disparity of industry payments in pediatric dermatology are worthy of further study.

More than just a stye: identifying seasonal patterns using google trends, and a review of infodemiological literature in ophthalmology.

PURPOSE: We aim to evaluate the utility of internet search query data in ophthalmology by: (1) Evaluating trends in searches for styes in the United States and worldwide, and (2) Performing a review of literature of infodemiological data in ophthalmology. METHODS: Google Trends search data for "stye" was analyzed from January 2004 to January 2020 in the United States and worldwide. Spearman's correlation coefficient and sinusoidal modeling were performed to assess the significance and seasonality of trends. Review of literature included searches for "ophthalmology Google trends," "ophthalmology twitter trends," "ophthalmology infodemiology," "eye google trends," and "social media ophthalmology." RESULTS: Searches for styes were cyclical in the United States and globally with a steady increase from 2004 to 2020 (sum-of-squares F-test for sinusoidal model: p < .0001, r2 = 0.96). Peak search volume index (SVI) months were 7.9 months in the United States and 6.8 months worldwide. U.S. temperature and SVI for stye were correlated in the United States at the state, divisional, and country-wide levels (p < .005; p < .005; p < .01 respectively). Seven articles met our literature review inclusion criteria. CONCLUSIONS: We present a novel finding of seasonality with global and U.S. searches for stye, and association of searches with temperature in the United States. Within ophthalmology, infodemiological literature has been used to track trends and identify seasonal disease patterns, perform disease surveillance, improve resource optimization by identifying regional hotspots, tailor marketing, and monitor institutional reputation. Future research into this domain may help identify further trends, improve prevention efforts, and reduce medical costs.

Clonal Vγ6+Vδ4+ T cells promote IL-17-mediated immunity against Staphylococcus aureus skin infection.

T cell cytokines contribute to immunity against Staphylococcus aureus, but the predominant T cell subsets involved are unclear. In an S. aureus skin infection mouse model, we found that the IL-17 response was mediated by γδ T cells, which trafficked from lymph nodes to the infected skin to induce neutrophil recruitment, proinflammatory cytokines IL-1α, IL-1ß, and TNF, and host defense peptides. RNA-seq for TRG and TRD sequences in lymph nodes and skin revealed a single clonotypic expansion of the encoded complementarity-determining region 3 amino acid sequence, which could be generated by canonical nucleotide sequences of TRGV5 or TRGV6 and TRDV4 However, only TRGV6 and TRDV4 but not TRGV5 sequences expanded. Finally, Vγ6+ T cells were a predominant γδ T cell subset that produced IL-17A as well as IL-22, TNF, and IFNγ, indicating a broad and substantial role for clonal Vγ6+Vδ4+ T cells in immunity against S. aureus skin infections.

Syndecan-1 Regulates Psoriasiform Dermatitis by Controlling Homeostasis of IL-17-Producing γδ T Cells.

IL-17 is a potent proinflammatory cytokine that drives pathogenesis of multiple autoimmune diseases, including psoriasis. A major source of pathogenic IL-17 is a subset of γδ T cells (Tγδ17) that acquires the ability to produce IL-17 while developing in the thymus. The mechanisms that regulate homeostasis of Tγδ17 cells and their roles in psoriasis, however, are not fully understood. In this paper, we show that the heparan sulfate proteoglycan syndecan-1 (sdc1) plays a critical role in regulating homeostasis of Tγδ17 cells and modulating psoriasis-like skin inflammation in mice. sdc1 was predominantly expressed by Tγδ17 cells (but not IL-17- Tγδ cells) in the thymus, lymph nodes, and dermis. sdc1 deficiency significantly and selectively increased the frequency and absolute numbers of Tγδ17 cells by mechanisms that included increased proliferation and decreased apoptosis. Adoptive transfer experiments ruled out a significant role of sdc1 expressed on nonhematopoietic cells in halting expansion and proliferation of sdc1-deficient Tγδ17 cells. When subjected to imiquimod-induced psoriasiform dermatitis, Tγδ17 cells in sdc1KO mice displayed heightened responses accompanied by significantly increased skin inflammation than their wild-type counterparts. Furthermore, transferred sdc1-deficient γδ T cells caused more severe psoriasiform dermatitis than their sdc1-sufficient counterparts in TCR-ßδ KO hosts. The results uncover a novel role for sdc1 in controlling homeostasis of Tγδ17 cells and moderating host responses to psoriasis-like inflammation.

Seasonal variability in public searches of keratosis pilaris: How the internet can illuminate a pattern in public interest.

In this study, we examine keratosis pilaris search patterns using Google Trends to determine any seasonality. Monthly searches were collected from January 2004 to January 2020 using "keratosis pilaris" as the search term in the Google Trends database. The US search data were compared to monthly temperatures and tested for correlation. Worldwide search interest was also acquired and, along with the US data, a two-model analysis was performed to determine any seasonal patterns. Peaks in search interest closely overlapped with higher temperatures in the United States and showed correlation (.44; P < .0001). The US and worldwide search interest also exhibited seasonality, which was confirmed with a sinusoidal regression being the best-fit model (R2 = .867 and .895). These results show higher search volume during warmer months in the United States and a clear cyclical pattern in searches worldwide and in the United States. Examination of these trends could elucidate peaks that health care providers may not have been aware of yielding improved resource allocation and preparedness for larger volume periods. This information in conjunction with clinical data could also shed more light in the future on potential peak seasons of incidence and prevalence.

Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1α release.

BACKGROUND: Atopic dermatitis (AD) is associated with epidermal barrier defects, dysbiosis, and skin injury caused by scratching. In particular, the barrier-defective epidermis in patients with AD with loss-of-function filaggrin mutations has increased IL-1α and IL-1ß levels, but the mechanisms by which IL-1α, IL-1ß, or both are induced and whether they contribute to the aberrant skin inflammation in patients with AD is unknown. OBJECTIVE: We sought to determine the mechanisms through which skin injury, dysbiosis, and increased epidermal IL-1α and IL-1ß levels contribute to development of skin inflammation in a mouse model of injury-induced skin inflammation in filaggrin-deficient mice without the matted mutation (ft/ft mice). METHODS: Skin injury of wild-type, ft/ft, and myeloid differentiation primary response gene-88-deficient ft/ft mice was performed, and ensuing skin inflammation was evaluated by using digital photography, histologic analysis, and flow cytometry. IL-1α and IL-1ß protein expression was measured by means of ELISA and visualized by using immunofluorescence and immunoelectron microscopy. Composition of the skin microbiome was determined by using 16S rDNA sequencing. RESULTS: Skin injury of ft/ft mice induced chronic skin inflammation involving dysbiosis-driven intracellular IL-1α release from keratinocytes. IL-1α was necessary and sufficient for skin inflammation in vivo and secreted from keratinocytes by various stimuli in vitro. Topical antibiotics or cohousing of ft/ft mice with unaffected wild-type mice to alter or intermix skin microbiota, respectively, resolved the skin inflammation and restored keratinocyte intracellular IL-1α localization. CONCLUSIONS: Taken together, skin injury, dysbiosis, and filaggrin deficiency triggered keratinocyte intracellular IL-1α release that was sufficient to drive chronic skin inflammation, which has implications for AD pathogenesis and potential therapeutic targets.

Colorectal cancer-global burden, trends, and geographical variations.

BACKGROUND: The aim of this study is to describe the trends and variations in the global burden of colorectal cancer (CRC). METHODS: Data (2012-2030) relating to CRC was extracted from GLOBOCAN 2012 database and analyzed. RESULTS: The results of our study demonstrate a rising global burden of colorectal cancer which persists until the year 2035 and likely beyond. The rise in the global burden is not uniform with significant variations influenced by geographic location, socio-economic status, age, and gender. Although the EURO region has the highest burden, Asia as a continent continues to bear the heaviest brunt of the disease. Although the burden of disease is higher in more developed regions, mortality is considerably higher in less developed regions and this gap widens over the next two decades. The disease predominantly affects the male gender across all regions of the world. Age has a complex relation with the burden of CRC and is affected by the cross-influences relating to socio-economic status. CONCLUSIONS: The results of our study demonstrate a rising global burden of CRC with some unique variations. Knowledge of this data can increase awareness and help strategic targeting of efforts and resources.

Global trends in esophageal cancer.

BACKGROUND AND OBJECTIVES: Esophageal Cancer (EC) is a lethal malignancy with poor prognosis and significant variations in the incidence, mortality, and histopathology based on geographic regions. The aim of this study was to quantitatively analyze these variations to identify patterns and areas for further research. METHODS: We utilized the GLOBOCAN 2012, and Cancer Incidence in five Continents, Volume X (CI5X) database to analyze variations in EC incidence and mortality. RESULTS: We found the EC incidence and mortality is geographically varied with a particularly high burden in East Asia and Eastern/Southern Africa where esophageal squamous cell carcinoma (SCC) predominates over adenocarcinoma (AC). Interestingly, there is a dichotomy between the high incidence of esophageal SCC in East Africa and low incidence in West Africa. The global incidence and mortality from EC is expected to rise in the coming decades. Asia, and China in particular, will continue to be the areas most burdened by EC, while Africa is expected to surpass the incidence and mortality rates of Europe. CONCLUSIONS: The global burden of EC is expected to rise in the coming years. Understanding the geographic, environmental, and genetic contributors to the development of EC will be essential in combating its prevalence.

Global epidemiological trends and variations in the burden of gallbladder cancer.

BACKGROUND: The aim of this study is to describe the trends and variations in the global burden of gallbladder cancer (GBC) with an emphasis on geographic variations and female gender. METHODS: Data (2012-2030) relating to GBC was extracted from GLOBOCAN 2012 database and analyzed. RESULTS: The results of our study document a rising global burden of GBC with geographic and gender variations. The highest burden was noted in the WPRO region (based on WHO regions), Asia (based on continents) and India, Chile, and China (based on countries). The less developed regions of the world account for the majority of the global burden of GBC. The geographic variations are also present within individual countries such as in India and Chile. Females are afflicted at a much higher rate with GBC and this predilection is exaggerated in countries with higher incidence such as India and Chile. In females, people of certain ethnic groups and lower socio-economic standing are at a higher risk. CONCLUSIONS: Our study demonstrates a rising global burden of GBC with some specific data on geographic and gender-based variations which can be used to develop strategies at the global as well as the high-risk individual country level.

Predictive global trends in the incidence and mortality of pancreatic cancer based on geographic location, socio-economic status, and demographic shift.

BACKGROUND AND OBJECTIVES: Pancreatic Cancer (PC) is a lethal malignancy that accounts for about 4% of cancer-related deaths worldwide. The aim of this study is to describe the influence of geography (based on WHO regions), socio-economic development (based on Human Development Index [HDI]) and demographic shift on the temporal trends in global incidence and mortality of PC. METHODS: Data (2012-2030) relating to the incidence, mortality of PC and demographic shifts based on WHO regions and HDI areas were extracted from GLOBOCAN 2012. Linear regression was used to evaluate trends in total incidence and mortality. RESULTS: We noted a definite association between PC and higher socio-economic status. Advanced age (age ≥65) contributed to the rising burden in all socio-economic regions of the world except in the Low Human Development (LHD) countries where the disease predominantly affected population <65 years of age. CONCLUSIONS: The global burden of PC is expected to rise significantly over the next few decades regardless of geographic location, socio-economic development, age and gender. Advance knowledge of this data can help formulate strategies to specifically target countries and populations that promote public health policy to tackle this lethal disease on the global stage. J. Surg. Oncol. 2016;114:736-742. © 2016 Wiley Periodicals, Inc.

A cross-sectional analysis of medications used by patients reporting alopecia areata on the FDA adverse events reporting system.

BACKGROUND: Alopecia areata (AA) is an autoimmune condition that leads to patchy, nonscarring hair loss. Its etiology remains unknown; the condition can be debilitating for patients, impacting their psychosocial wellbeing. Various triggers have been reported, ranging from genetic predisposition and infections to environmental factors. Medications have also been thought to be an inciting factor in AA. METHODS: Using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), all cases reporting AA as an adverse event were used to capture associated medications and patient characteristics. RESULTS: There were 1,331 AA cases reported as an adverse event with medication use. Monoclonal antibodies accounted for 6 out of the top 10 drugs associated with the highest number of AA cases. Males were more likely to report AA when taking adalimumab (OR: 1.79, P = 0.04) and dupilumab (OR: 2.56, P = 0.03) compared to females. Individuals between 42 and 64 years old accounted for 46.7% of AA cases. Lastly, females in older age groups showed greater odds of developing AA compared to males (OR: 1.03, P < 0.01). CONCLUSIONS: Based on the FAERS, there has been a steady rise in AA cases, and monoclonal antibodies were the most frequently cited medication class tied to AA. With a dearth of literature on triggers and patient demographics, we sought to describe features of AA cases that could increase awareness and be used to improve future clinical outcomes in patients.

The state of artificial intelligence for systemic dermatoses: Background and applications for psoriasis, systemic sclerosis, and much more.

Artificial intelligence (AI) has been steadily integrated into dermatology, with AI platforms already attempting to identify skin cancers and diagnose benign versus malignant lesions. Although not as widely known, AI programs have also been utilized as diagnostic and prognostic tools for dermatologic conditions with systemic or extracutaneous involvement, especially for diseases with autoimmune etiologies. We have provided a primer on commonly used AI platforms and the practical applicability of these algorithms in dealing with psoriasis, systemic sclerosis, and dermatomyositis as a microcosm for future directions in the field. With a rapidly changing landscape in dermatology and medicine as a whole, AI could be a versatile tool to support clinicians and enhance access to care.

The top 100 most cited Mohs micrographic surgery articles: an analysis of Altmetrics data from 2010 to 2020.

With skin cancer rates rising, there is a consistent stream of literature published on Mohs micrographic surgery (MMS). However, there are no studies examining MMS article visibility and readership patterns. The Altmetric Attention Score (AAS) is a metric that quantifies article distribution on media platforms. We analyzed the 100 most cited MMS publications from 2010 to 2020 and constructed multivariate regression models using top 25th percentile AASs and mentions on Facebook, Twitter, and new outlets as outcome variables. Articles with an AAS in the top 25th quartile consistently performed better with higher citations, Twitter mentions, Facebook mentions, and journal impact factors compared to articles in the lower three quartiles (53.8 vs 33.9; 4.68 vs 0.44; 0.32 vs 0.08; 53.5 vs 14.6; p < 0.05 for all). There were significantly lower female last authors versus males in the top quartile of AAS articles, with males 142 times more likely to have articles in the top quartile (p < 0.05). Studies comparing MMS to other surgical techniques and funded articles had higher odds of being in the top quartile of AASs (aOR 29.63 p < 0.05; aOR 74.50 p < 0.05). AASs can be useful to understand public interest, readership, and article features that influence the reach of MMS literature.

Interface fluid syndrome after LASIK surgery: retrospective pooled analysis and systematic review.

Interface fluid syndrome (IFS) is a complication associated with laser in situ keratomileusis (LASIK) surgery where a fluid pocket in the corneal stroma decreases visual acuity. A systematic review of IFS cases using PRISMA guidelines was performed yielding a total of 33 patients. 2 outcomes were selected for logistic regression analysis: final corrected distance visual acuity (CDVA) and need for surgical management. Results showed 33.3% of patients required surgery, 51.5% had their IFS resolve within 1 month or sooner, and 51.5% had final CDVA 20/25 or better. Higher presenting intraocular pressure (IOP) and duration of IFS ≤1 month was associated with higher odds of final CDVA 20/25 or better (adjusted odds ratio [aOR] 1.12, P = .04; aOR 7.71, P = .02, respectively). Endothelial cell dysfunction led to 17.55 greater odds for requiring surgical compared to medical management (aOR 0.36, P = .04). Presenting IOP and duration of IFS predicted final CDVA, while prior endothelial cell dysfunction predicted need for surgery.

Use of Hydroxychloroquine in Hair Disorders.

Hydroxychloroquine (HCQ) is an antimalarial that is utilized to treat a range of dermatologic and autoimmune disorders. With its ability to alter immunologic mechanisms, it has been used to slow or halt the progression of hair loss in conditions secondary to autoimmune dysfunction. Lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and alopecia areata (AA) are hair disorders with underlying autoimmune components and no standardized treatment guidelines. We summarized the available literature on the use of HCQ to treat LPP, FFA, and AA. For all three conditions, HCQ showed variable efficacy from halted hair loss to no improvement. While patients did show success with HCQ treatment, there were no clear treatment patterns. Regimens ranged from HCQ monotherapy to combination treatments with other agents like steroids. Overall, HCQ should certainly be considered by clinicians as a treatment option for patient suffering from these hair disorders. While there is no standardized treatment, incorporation of HCQ should take into consideration individual patient characteristics, clinical judgment, and risks of side effects.

Hydroxychloroquine (HCQ) is an antimalarial drug that acts on the immune system. Lichen planopilaris, frontal fibrosing alopecia, and alopecia areata are all disorders that result in hair loss secondary to immune dysfunction. HCQ has been used to treat these conditions, so publications addressing HCQ use for such hair loss disorders were collected, and the findings were summarized. Overall, HCQ showed mixed efficacy but can be a successful treatment option for some patients. Various treatment patterns were seen from using only HCQ to combination therapy plans with HCQ and steroids, for example. Treating these hair loss conditions can be challenging, and while there are no standardized guidelines, HCQ should be considered in the treatment arsenal for patients.

Missed games, financial losses, and characteristics of eye injuries in the National Basketball Association during the 2010-2011 to 2017-2018 seasons.

PURPOSE: The purpose is to report financial loss, demographic metrics, and mechanisms of injury associated with eye injuries in the National Basketball Association (NBA) from the 2010-2011 to 2017-2018 seasons. METHODS: We performed a retrospective review of eye injuries in the NBA from the 2010-2011 to 2017-2018 seasons using publicly available information from Basketball Reference and the Pro Sports Transactions websites. Only injuries of the eye and adnexa that caused players to miss games in the regular season and playoffs were included in the study. Financial loss was calculated based on the regular season salary of the players and normalized for inflation with 2018 as the base year. RESULTS: There were 30 eye injuries causing a total of 106 missed games and $7,486,770 in financial losses across eight seasons. Linear regressions showed a moderately positive increase in eye injuries (Pearson's r = 0.68, P = 0.07, and 0.79 injuries per year/1000 game-days increase) and financial losses (Pearson's r = 0.67, P = 0.07, and $185.75 increase per year/1000 game-days) over time. There were significantly more games missed due to orbital fractures than games missed due to contusions/lacerations (11.5 vs. 2.8 missed games, P = 0.01). CONCLUSION: We demonstrate an increasing trend of eye injuries in the NBA, resulting in increased financial loss. Injuries may be varied in type and affect the number of games missed.

Utility of diffusion-weighted imaging to differentiate benign and malignant solid orbital tumours.

OBJECTIVE: We assessed the utility of apparent diffusion coefficients (ADCs) derived from diffusion-weighted imaging to differentiate benign and malignant orbital tumours by oculoplastic surgeons in the clinical setting and sought to validate observed ADC cut-off values. DESIGN AND PARTICIPANTS: Retrospective review of patients with benign or malignant biopsy-confirmed orbital tumours. METHODS: Blinded graders including 2 oculoplastic surgeons, 1 neuroradiologist, and 1 medical student located and measured orbital tumour ADCs (10-6 mm2/s) using the Region of Interest tool. OUTCOME MEASURES: Nonradiologist measurements were compared with each other to assess reliability and with an expert neuroradiologist measurement and final pathology to assess accuracy. RESULTS: Twenty-nine orbital tumours met inclusion criteria, consisting of 6 benign tumours and 23 malignant tumours. Mean ADC values for benign orbital tumours were 1430.59 ± 254.81 and 798.68 ± 309.12 mm2/s for malignant tumours. Our calculated optimized ADC cut-off to differentiate benign from malignant orbital tumours was 1120.84 × 10-6 mm2/s (sensitivity 1, specificity 0.9). Inter-rater reliability was excellent (intraclass correlation coefficient = 0.92; 95% CI, 0.86-0.96). Our 3 graders had a combined accuracy of 84.5% (92.3%, 92.3%, and 65.4%). CONCLUSIONS: Our ADC cut-off of 1120.84 × 10-6 mm2/s for benign and malignant orbital tumours agrees with previously established values in literature. Without priming with instructions, training, or access to patient characteristics, most tumours were correctly classified using rapid ADC measurements. Surgeons without radiologic expertise can use the ADC tool to quickly risk stratify orbital tumours during clinic visits to guide patient expectations and further work-up.

IL-6R/Signal Transducer and Activator of Transcription 3 Signaling in Keratinocytes rather than in T Cells Induces Psoriasis-Like Dermatitis in Mice.

Signal transducer and activator of transcription 3 (STAT3) is important for psoriasis pathogenesis because STAT3 signaling downstream of IL-6, IL-21, IL-22, and IL-23 contributes to T helper type 17 cell development and because transgenic mice with keratinocyte (KC) STAT3 expression (K14-Stat3C mice) develop psoriasis-like dermatitis. In this study, the relative contribution of STAT3 signaling in KCs versus in T cells was evaluated in the imiquimod model of psoriasis-like dermatitis. Mice with STAT3-inducible deletion in KCs (K5-Stat3-/- mice) had decreased psoriasis-like dermatitis and epidermal STAT3 phosphorylation compared with wild-type mice, whereas mice with constitutive deletion of STAT3 in all T cells were similar to wild-type mice. Interestingly, mice with KC-inducible deletion of IL-6Rα had similar findings to those of K5-Stat3-/- mice, identifying IL-6/IL-6R as a predominant upstream signal for KC STAT3-induced psoriasis-like dermatitis. Moreover, psoriasis-like dermatitis inversely associated with type 1 immune gene products, especially CXCL10, whereas CXCL10 limited psoriasis-like dermatitis, suggesting that KC STAT3 signaling promoted psoriasis-like dermatitis by restricting downstream CXCL10 expression. Finally, treatment of mice with the pan-Jak inhibitor, tofacitinib, reduced psoriasis-like dermatitis and epidermal STAT3 phosphorylation. Taken together, STAT3 signaling in KCs rather than in T cells was a more important determinant for psoriasis-like dermatitis in a mechanism that involved upstream KC IL-6R signaling and downstream inhibition of type 1 immunity‒associated CXCL10 responses.