Abstract: Background: Cholecystitis is an inflammatory disease involving the gallbladder, often associated with digestive disorders and systemic immune response. This systemic immune response could potentially influence the immune status of the skin, particularly in conditions like dermatitis. Despite extensive research on dermatitis, the causal relationship between cholecystitis and dermatitis subtypes (DSs) remains unclear. Objective: The aim of this study was to investigate the causal relationship between cholecystitis and DSs. Methods: Two-sample Mendelian randomization (MR) was used to analyze the causal relationship between cholecystitis and DSs. We then utilized the Bayesian Weighted Mendelian Randomization (BWMR) method to validate our findings and applied bidirectional MR analysis to confirm the causal direction. After establishing the associations between traits, we delved into the underlying mechanisms of this interesting finding. Subsequently, we used 91 inflammatory proteins as mediators and performed summary data-based mendelian randomization (SMR) analysis to further investigate the pathogenesis of DSs. Results: MR results evidently showed that cholecystitis can significantly reduce the risk of allergic contact dermatitis (ACD) (IVW, OR=0.8834, p=0.0368) and exfoliative dermatitis (ED) (IVW, OR=0.5738, p=0.0126). BWMR also provided secondary validation of the casual associations. In the subsequent reverse direction MR analyses, reverse causality was not present, so cholecystitis had a unidirectional effect and existed as a protective factor for ACD and ED. Interestingly, cholecystitis appears to lower the risk of ACD and ED by downregulating IL-6, IL-7, and IFN-γ. Additionally, the genes HCG27 and HLA-DRB5 may play a significant role in the pathogenesis of ACD. Conclusion: This study used a two-step MR analysis of genetic summary data to investigate to what extent inflammatory proteins impact the protective role of cholecystitis on dermatitis. We also identified several proteins and genes that could serve as potential drug targets.
{"title":"A Two-step Bayesian Mendelian Randomization Study on Cholecystitis and Dermatitis","authors":"Chenyu Zhao, Changqian Cen, Ruihan Zhang, Wenjin He, Yiyang Jiao, Zhuoya Chen, Zhaoqi Wu, Ting Luan","doi":"10.1101/2024.09.17.24313850","DOIUrl":"https://doi.org/10.1101/2024.09.17.24313850","url":null,"abstract":"Abstract:\u0000Background: Cholecystitis is an inflammatory disease involving the gallbladder, often associated with digestive disorders and systemic immune response. This systemic immune response could potentially influence the immune status of the skin, particularly in conditions like dermatitis. Despite extensive research on dermatitis, the causal relationship between cholecystitis and dermatitis subtypes (DSs) remains unclear. Objective: The aim of this study was to investigate the causal relationship between cholecystitis and DSs.\u0000Methods: Two-sample Mendelian randomization (MR) was used to analyze the causal relationship between cholecystitis and DSs. We then utilized the Bayesian Weighted Mendelian Randomization (BWMR) method to validate our findings and applied bidirectional MR analysis to confirm the causal direction. After establishing the associations between traits, we delved into the underlying mechanisms of this interesting finding. Subsequently, we used 91 inflammatory proteins as mediators and performed summary data-based mendelian randomization (SMR) analysis to further investigate the pathogenesis of DSs.\u0000Results: MR results evidently showed that cholecystitis can significantly reduce the risk of allergic contact dermatitis (ACD) (IVW, OR=0.8834, p=0.0368) and exfoliative dermatitis (ED) (IVW, OR=0.5738, p=0.0126). BWMR also provided secondary validation of the casual associations. In the subsequent reverse direction MR analyses, reverse causality was not present, so cholecystitis had a unidirectional effect and existed as a protective factor for ACD and ED. Interestingly, cholecystitis appears to lower the risk of ACD and ED by downregulating IL-6, IL-7, and IFN-γ. Additionally, the genes HCG27 and HLA-DRB5 may play a significant role in the pathogenesis of ACD.\u0000Conclusion: This study used a two-step MR analysis of genetic summary data to investigate to what extent inflammatory proteins impact the protective role of cholecystitis on dermatitis. We also identified several proteins and genes that could serve as potential drug targets.","PeriodicalId":501385,"journal":{"name":"medRxiv - Dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1101/2024.09.16.24313743
Lee Wheless, Ranya Guennoun, Basia M Michalski, Katlyn M Gonzalez, Rachel Weiss, Siwei Zhang, Lydia Yao, Christopher Madden, Hua-Chang Chen, Jefferson Triozzi, Ran Tao, Otis D Wilson, Quinn S Wells, Adriana M Hung, Kristin Bibee, Rebecca I Hartman, Yaomin Xu, Million Veteran Program
IMPORTANCE. Nicotinamide metabolites have recently been implicated in increased risk of major cardiovascular events (MACE). Supportive data about clinical risk of MACE for nicotinamide users is lacking. OBJECTIVE. To determine whether nicotinamide use results in an increase of MACE. DESIGN, SETTING, PARTICIPANTS. Retrospective cohort study of two patient cohorts, Vanderbilt University Medical Center (VUMC) and Military Veteran Program (MVP). The risk of MACE in patients exposed to nicotinamide was compared to the risk of MACE in unexposed patients. In the VUMC cohort, 1228 patients were exposed to nicotinamide based on keyword entry for 'nicotinamide' or 'niacinamide' and hand-review of charts, while 253 were unexposed but had documented recommendation for use. In the MVP cohort, there were 1594 with exposure to nicotinamide propensity score matched to 2694 without exposure. EXPOSURES. The primary exposure for the VUMC cohort was a confirmed exposure to nicotinamide in chart review. The primary exposure for the MVP cohort was medication entry for 'nicotinamide' or 'niacinamide'. MAIN OUTCOME(S) AND MEASURE(S). The primary outcome was development of MACE based on a validated phenotype. RESULTS. Between both cohorts, 6039 patients were included, of whom 5125 were male with a mean age of 63.2 years. Neither cohort had significant differences in mean age, sex, race and ethnicity between the nicotinamide exposed and unexposed groups. In the VUMC cohort, there was no significant association between nicotinamide exposure and the primary outcome of MACE (HR 0.76, 95% CI 0.46 - 1.25, p = 0.28). MACE prior to nicotinamide exposure was strongly associated with subsequent MACE (HR 9.01, 95% CI 5.90 - 13.70, p < 0.001). In the MVP cohort, we adjusted for MACE risk factors as potential confounding variables and saw no significant association between nicotinamide exposure and MACE (HR 1.00 95% CI 0.75 - 1.32), while history of prior MACE remained strongly associated with subsequent MACE (HR 9.50, 95% CI 6.38 - 14.1). CONCLUSIONS AND RELEVANCE. In this retrospective cohort study of 6039 adults from two different patient populations, we found no increased risk of MACE in patients with nicotinamide exposure.
{"title":"Risk of Major Adverse Cardiovascular Events following Nicotinamide Exposure: Cohort Study","authors":"Lee Wheless, Ranya Guennoun, Basia M Michalski, Katlyn M Gonzalez, Rachel Weiss, Siwei Zhang, Lydia Yao, Christopher Madden, Hua-Chang Chen, Jefferson Triozzi, Ran Tao, Otis D Wilson, Quinn S Wells, Adriana M Hung, Kristin Bibee, Rebecca I Hartman, Yaomin Xu, Million Veteran Program","doi":"10.1101/2024.09.16.24313743","DOIUrl":"https://doi.org/10.1101/2024.09.16.24313743","url":null,"abstract":"IMPORTANCE. Nicotinamide metabolites have recently been implicated in increased risk of major cardiovascular events (MACE). Supportive data about clinical risk of MACE for nicotinamide users is lacking.\u0000OBJECTIVE. To determine whether nicotinamide use results in an increase of MACE.\u0000DESIGN, SETTING, PARTICIPANTS. Retrospective cohort study of two patient cohorts, Vanderbilt University Medical Center (VUMC) and Military Veteran Program (MVP). The risk of MACE in patients exposed to nicotinamide was compared to the risk of MACE in unexposed patients. In the VUMC cohort, 1228 patients were exposed to nicotinamide based on keyword entry for 'nicotinamide' or 'niacinamide' and hand-review of charts, while 253 were unexposed but had documented recommendation for use. In the MVP cohort, there were 1594 with exposure to nicotinamide propensity score matched to 2694 without exposure. EXPOSURES. The primary exposure for the VUMC cohort was a confirmed exposure to nicotinamide in chart review. The primary exposure for the MVP cohort was medication entry for 'nicotinamide' or 'niacinamide'. MAIN OUTCOME(S) AND MEASURE(S). The primary outcome was development of MACE based on a validated phenotype.\u0000RESULTS. Between both cohorts, 6039 patients were included, of whom 5125 were male with a mean age of 63.2 years. Neither cohort had significant differences in mean age, sex, race and ethnicity between the nicotinamide exposed and unexposed groups. In the VUMC cohort, there was no significant association between nicotinamide exposure and the primary outcome of MACE (HR 0.76, 95% CI 0.46 - 1.25, p = 0.28). MACE prior to nicotinamide exposure was strongly associated with subsequent MACE (HR 9.01, 95% CI 5.90 - 13.70, p < 0.001). In the MVP cohort, we adjusted for MACE risk factors as potential confounding variables and saw no significant association between nicotinamide exposure and MACE (HR 1.00 95% CI 0.75 - 1.32), while history of prior MACE remained strongly associated with subsequent MACE (HR 9.50, 95% CI 6.38 - 14.1). CONCLUSIONS AND RELEVANCE. In this retrospective cohort study of 6039 adults from two different patient populations, we found no increased risk of MACE in patients with nicotinamide exposure.","PeriodicalId":501385,"journal":{"name":"medRxiv - Dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1101/2024.09.12.24313560
David Robert Grimes
The advent of mass-market Light Emitting Diodes (LEDs) has seen considerable interest in potential dermatological applications of LED light photobiomodulation (PBM) for a range of conditions, with a thriving market for direct-to-consumer LED treatments, including red light, blue light, and yellow light wavelengths. Evidence of efficacy for many conditions is however decidedly mixed, with starkly different outcomes reported by different authors. Due to the wide range of irradiances and wavelengths used, interpretation, comparison, and even efficacy evaluation is often impossible or prohibitive, impeding evidence synthesis. This work establishes a framework for objectively cross-comparing patient dose in terms of fluence, and a model for contrasting received dose to typical solar dose at ground level to facilitate interpretation of results and evidence synthesis. This allowes direct cross-comparison of patient skin fluence from LED PMB treatments under different regimes, and a means for evidence synthesis. This was applied to LED PMB data from 27 clinical trials to examine fluences and patient-equivalent solar exposure from LED light-sources for dermatological conditions, including acne vulgaris, wrinkle-reduction, wound-healing, psoriasis severity, and erythemal index. The results of this analysis suggest that fluences, wavelengths, and solar exposure equivalent differed by orders of magnitude in he studies analysed, with effective doses often comparable to typical daily solar exposure. Better dose quantification and plausible biological justification for various wavelengths and fluences are imperative if LED therapy studies for dermatology are to be informative and research replicability improved.
随着发光二极管（LED）进入大众市场，人们对 LED 光生物调节（PBM）在皮肤病领域的潜在应用产生了浓厚的兴趣，包括红光、蓝光和黄光波长在内的直接面向消费者的 LED 治疗市场蓬勃发展。然而，许多病症的疗效证据明显参差不齐，不同作者报告的结果也截然不同。由于所使用的辐照度和波长范围很广，解释、比较甚至疗效评估通常都是不可能的或令人望而却步的，从而阻碍了证据的综合。这项工作建立了一个以通量为单位对患者剂量进行客观交叉比较的框架，以及一个将接收到的剂量与地面典型太阳剂量进行对比的模型，以方便对结果进行解释和证据综合。这样就可以直接交叉比较不同制度下 LED PMB 治疗产生的患者皮肤通量，并提供证据综合的方法。我们将这一方法应用于 27 项临床试验的 LED PMB 数据，以检查 LED 光源治疗皮肤病（包括寻常痤疮、除皱、伤口愈合、牛皮癣严重程度和红斑指数）的通量和患者等效太阳照射。这项分析的结果表明，在所分析的研究中，流度、波长和太阳照射当量相差几个数量级，有效剂量通常与典型的日常太阳照射相当。如果要使皮肤病学的 LED 治疗研究具有参考价值并提高研究的可复制性，就必须对各种波长和荧光进行更好的剂量量化和合理的生物学论证。
{"title":"Methodological issues in visible LED therapy dermatological research and reporting","authors":"David Robert Grimes","doi":"10.1101/2024.09.12.24313560","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313560","url":null,"abstract":"The advent of mass-market Light Emitting Diodes (LEDs) has seen considerable interest in potential dermatological applications of LED light photobiomodulation (PBM) for a range of conditions, with a thriving market for direct-to-consumer LED treatments, including red light, blue light, and yellow light wavelengths. Evidence of efficacy for many conditions is however decidedly mixed, with starkly different outcomes reported by different authors. Due to the wide range of irradiances and wavelengths used, interpretation, comparison, and even efficacy evaluation is often impossible or prohibitive, impeding evidence synthesis. This work establishes a framework for objectively cross-comparing patient dose in terms of fluence, and a model for contrasting received dose to typical solar dose at ground level to facilitate interpretation of results and evidence synthesis. This allowes direct cross-comparison of patient skin fluence from LED PMB treatments under different regimes, and a means for evidence synthesis. This was applied to LED PMB data from 27 clinical trials to examine fluences and patient-equivalent solar exposure from LED light-sources for dermatological conditions, including acne vulgaris, wrinkle-reduction, wound-healing, psoriasis severity, and erythemal index. The results of this analysis suggest that fluences, wavelengths, and solar exposure equivalent differed by orders of magnitude in he studies analysed, with effective doses often comparable to typical daily solar exposure. Better dose quantification and plausible biological justification for various wavelengths and fluences are imperative if LED therapy studies for dermatology are to be informative and research replicability improved.","PeriodicalId":501385,"journal":{"name":"medRxiv - Dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vitiligo, a dermatological condition characterized by depigmented patches on the skin, affects up to 2% of the global population. Its management is complex, often hindered by delayed diagnosis due to limited access to dermatologists and/ digital tools. Recent advancements in machine learning (ML) offer a potential solution by providing digital tools for early detection and management. This proof-of-concept study describes the development of a machine learning pipeline integrated into a mobile application for vitiligo assessment.
{"title":"Leveraging Machine Learning & Mobile Application Technology for Vitiligo Management: A Proof-of-Concept","authors":"Mahla Abdolahnejad, Hyerin Jeong, Victoria Lin, Tiffany Ng, Emad Altaki, Anthea Mo, Burak Yildiz, Hannah O. Chan, Collin Hong, Rakesh Joshi","doi":"10.1101/2024.09.06.24313068","DOIUrl":"https://doi.org/10.1101/2024.09.06.24313068","url":null,"abstract":"Vitiligo, a dermatological condition characterized by depigmented patches on the skin, affects up to 2% of the global population. Its management is complex, often hindered by delayed diagnosis due to limited access to dermatologists and/ digital tools. Recent advancements in machine learning (ML) offer a potential solution by providing digital tools for early detection and management. This proof-of-concept study describes the development of a machine learning pipeline integrated into a mobile application for vitiligo assessment.","PeriodicalId":501385,"journal":{"name":"medRxiv - Dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1101/2024.08.28.24311481
Songchun Yang, Dilan Deng, Wenrui Lin, Xiaozhen Chen, Shuang Zhao, Lixia Lu, Yi Xiao, Minxue Shen, Mingliang Chen, Xiang Chen, Juan Su
Introduction A patient registry database is an important tool to address a wide range of research questions. Several countries have established nationwide melanoma registry databases. However, there is no report on summarising and comparing these databases. This scoping review aims to answer a broad question on how contemporary nationwide melanoma registry databases were conducted across different countries.
{"title":"Nationwide melanoma registry databases in real-world settings: a scoping review protocol","authors":"Songchun Yang, Dilan Deng, Wenrui Lin, Xiaozhen Chen, Shuang Zhao, Lixia Lu, Yi Xiao, Minxue Shen, Mingliang Chen, Xiang Chen, Juan Su","doi":"10.1101/2024.08.28.24311481","DOIUrl":"https://doi.org/10.1101/2024.08.28.24311481","url":null,"abstract":"<strong>Introduction</strong> A patient registry database is an important tool to address a wide range of research questions. Several countries have established nationwide melanoma registry databases. However, there is no report on summarising and comparing these databases. This scoping review aims to answer a broad question on how contemporary nationwide melanoma registry databases were conducted across different countries.","PeriodicalId":501385,"journal":{"name":"medRxiv - Dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1101/2024.08.23.24312506
Cristina Guadalupe Beltran Munoz, Elissa Bracamontes Perez, Fernanda Corrales Bay, Aimee Adriana Barajas Nieto, Kate Georgette Rojo Navarro
Introduction: Minimally invasive cosmetic procedures are medical interventions that do not involve the use of surgical incisions. They are usually based on the administration of biocompatible compounds into subcutaneous or dermal tissue. Although considered low-risk, they can have significant adverse effects such as tissue damage or occlusion of superficial blood vessels. Describing their complications is necessary to ensure the responsible use of these resources. Objective: To describe the adverse effects secondary to the use of minimally invasive cosmetic procedures. Materials and Methods: Studies describing the adverse effects of minimally invasive cosmetic procedures were searched in PubMed, Scopus, Embase, and Google Scholar from January 2012 to December 2023. Results: A total of 98 articles were included. The administration of hyaluronic acid, botulinum toxin, silicone, and autologous fat grafts were the most commonly used procedures. Local symptoms were the most commonly reported reactions (53 studies). Meanwhile, temporary or permanent blindness was reported in 10 studies, immunological alterations in 8, severe pulmonary involvement in 6, neurological damage in 5, arterial occlusion in 3, and 2 studies reported fatalities. Conclusion: Minimally invasive cosmetic procedures can cause local complications in the majority of cases, but they can also lead to fatal outcomes, particularly in unprofessional settings. Undergoing these techniques requires a comprehensive professional assessment and close follow-up by licensed personnel.
{"title":"Comprehensive Review of Adverse Effects in Minimally Invasive Cosmetic Procedures: Insights from a Decade of Clinical Data","authors":"Cristina Guadalupe Beltran Munoz, Elissa Bracamontes Perez, Fernanda Corrales Bay, Aimee Adriana Barajas Nieto, Kate Georgette Rojo Navarro","doi":"10.1101/2024.08.23.24312506","DOIUrl":"https://doi.org/10.1101/2024.08.23.24312506","url":null,"abstract":"Introduction: Minimally invasive cosmetic procedures are medical interventions that do not involve the use of surgical incisions. They are usually based on the administration of biocompatible compounds into subcutaneous or dermal tissue. Although considered low-risk, they can have significant adverse effects such as tissue damage or occlusion of superficial blood vessels. Describing their complications is necessary to ensure the responsible use of these resources. Objective: To describe the adverse effects secondary to the use of minimally invasive cosmetic procedures. Materials and Methods: Studies describing the adverse effects of minimally invasive cosmetic procedures were searched in PubMed, Scopus, Embase, and Google Scholar from January 2012 to December 2023. Results: A total of 98 articles were included. The administration of hyaluronic acid, botulinum toxin, silicone, and autologous fat grafts were the most commonly used procedures. Local symptoms were the most commonly reported reactions (53 studies). Meanwhile, temporary or permanent blindness was reported in 10 studies, immunological alterations in 8, severe pulmonary involvement in 6, neurological damage in 5, arterial occlusion in 3, and 2 studies reported fatalities. Conclusion: Minimally invasive cosmetic procedures can cause local complications in the majority of cases, but they can also lead to fatal outcomes, particularly in unprofessional settings. Undergoing these techniques requires a comprehensive professional assessment and close follow-up by licensed personnel.","PeriodicalId":501385,"journal":{"name":"medRxiv - Dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.1101/2024.08.22.24312403
Juan Ignacio Pisula, Doris Helbig, Lucas Sancere, Oana-Diana Persa, Corinna Burger, Anne Frolich, Carina Lorenz, Sandra Bingmann, Dennis Niebel, Konstantin Drexler, Jennifer Landsberg, Roman Thomas, Katarzyna Bozek, Johannes Bragelmann
Predicting cancer patient disease progression is a key step towards personalized medicine and secondary prevention. The ability to predict which patients are at an elevated risk of developing local recurrences or metastases would allow for tailored surveillance of these high-risk patients as well as enhanced and timely interventions. We developed a deep learning transformer-based approach for prediction of progression of cutaneous squamous cell carcinoma (cSCC) patients based on diagnostic histopathology slides of the tumor. Our model, trained in a federated manner on patient cohorts from three clinical centers, reached an accuracy of AUROC=0.82, surpassing the predictive power of clinico-pathological parameters used to assess progression risk. We conducted an interpretability analysis, systematically comparing a broad range of spatial and morphological features that characterize tissue regions predictive of patient progression. Our findings suggest that information located at the tumor boundaries is predictive of patient progression and that heterogeneity of tissue morphology and organization are characteristic of progressive cSCCs. Trained in a federated fashion exclusively on standard diagnostic slides obtained during routine care of cSCC patients, our model can be deployed and expanded across other clinical centers. This approach thereby offers a potentially powerful tool for improved screening and thus better clinical management of cSCC patients.
{"title":"Explainable, federated deep learning model predicts disease progression risk of cutaneous squamous cell carcinoma","authors":"Juan Ignacio Pisula, Doris Helbig, Lucas Sancere, Oana-Diana Persa, Corinna Burger, Anne Frolich, Carina Lorenz, Sandra Bingmann, Dennis Niebel, Konstantin Drexler, Jennifer Landsberg, Roman Thomas, Katarzyna Bozek, Johannes Bragelmann","doi":"10.1101/2024.08.22.24312403","DOIUrl":"https://doi.org/10.1101/2024.08.22.24312403","url":null,"abstract":"Predicting cancer patient disease progression is a key step towards personalized medicine and secondary prevention. The ability to predict which patients are at an elevated risk of developing local recurrences or metastases would allow for tailored surveillance of these high-risk patients as well as enhanced and timely interventions. We developed a deep learning transformer-based approach for prediction of progression of cutaneous squamous cell carcinoma (cSCC) patients based on diagnostic histopathology slides of the tumor. Our model, trained in a federated manner on patient cohorts from three clinical centers, reached an accuracy of AUROC=0.82, surpassing the predictive power of clinico-pathological parameters used to assess progression risk. We conducted an interpretability analysis, systematically comparing a broad range of spatial and morphological features that characterize tissue regions predictive of patient progression. Our findings suggest that information located at the tumor boundaries is predictive of patient progression and that heterogeneity of tissue morphology and organization are characteristic of progressive cSCCs. Trained in a federated fashion exclusively on standard diagnostic slides obtained during routine care of cSCC patients, our model can be deployed and expanded across other clinical centers. This approach thereby offers a potentially powerful tool for improved screening and thus better clinical management of cSCC patients.","PeriodicalId":501385,"journal":{"name":"medRxiv - Dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19DOI: 10.1101/2024.08.16.24312116
Lauri Heiskanen, Liisa Nissinen, Elina Siljamaki, Jaakko Knuutila, Teijo Pellinen, Markku Kallajoki, Jyrki Heino, Pilvi Riihila, Veli-Matti Kahari
Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and the metastatic disease is associated with poor prognosis. We have examined the role of complement C5a receptor, C5aR1, in the progression and metastasis of cSCC. C5aR1 expression was increased in cSCC cells in 3D spheroid coculture model in the presence of fibroblasts, and that treatment with recombinant C5a enhanced the invasion of cSCC cells. Staining for C5aR1 was detected on the surface of tumor cells at the invasive edge of human cSCC xenografts in vivo. Staining of metastatic and nonmetastatic primary human cSCCs, premalignant and benign epidermal lesions and normal skin for C5aR1 with multiplex immunofluorescence and chromogenic immunohistochemistry revealed increased expression of C5aR1 on the surface of tumor cells and fibroblasts in invasive cSCCs and recessive dystrophic epidermolysis bullosa associated cSCCs compared to cSCC in situ, actinic keratoses, seborrheic keratoses and normal skin. Increased expression of C5aR1 on the tumor cell surface and in fibroblasts was associated with metastatic risk and poor disease specific survival of patients with primary cSCC. These findings reveal the role of C5aR1 in cSCC invasion and identify C5aR1 as a novel biomarker for metastasis risk and poor prognosis in patients with cSCC. The results also suggest that C5aR1 could be a novel therapeutic target for treatment of locally advanced and metastatic cSCC.
{"title":"Expression of C5aR1 in Cutaneous Squamous Cell Carcinoma is Associated with Invasion, Metastasis and Poor Prognosis","authors":"Lauri Heiskanen, Liisa Nissinen, Elina Siljamaki, Jaakko Knuutila, Teijo Pellinen, Markku Kallajoki, Jyrki Heino, Pilvi Riihila, Veli-Matti Kahari","doi":"10.1101/2024.08.16.24312116","DOIUrl":"https://doi.org/10.1101/2024.08.16.24312116","url":null,"abstract":"Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and the metastatic disease is associated with poor prognosis. We have examined the role of complement C5a receptor, C5aR1, in the progression and metastasis of cSCC. C5aR1 expression was increased in cSCC cells in 3D spheroid coculture model in the presence of fibroblasts, and that treatment with recombinant C5a enhanced the invasion of cSCC cells. Staining for C5aR1 was detected on the surface of tumor cells at the invasive edge of human cSCC xenografts in vivo. Staining of metastatic and nonmetastatic primary human cSCCs, premalignant and benign epidermal lesions and normal skin for C5aR1 with multiplex immunofluorescence and chromogenic immunohistochemistry revealed increased expression of C5aR1 on the surface of tumor cells and fibroblasts in invasive cSCCs and recessive dystrophic epidermolysis bullosa associated cSCCs compared to cSCC in situ, actinic keratoses, seborrheic keratoses and normal skin. Increased expression of C5aR1 on the tumor cell surface and in fibroblasts was associated with metastatic risk and poor disease specific survival of patients with primary cSCC. These findings reveal the role of C5aR1 in cSCC invasion and identify C5aR1 as a novel biomarker for metastasis risk and poor prognosis in patients with cSCC. The results also suggest that C5aR1 could be a novel therapeutic target for treatment of locally advanced and metastatic cSCC.","PeriodicalId":501385,"journal":{"name":"medRxiv - Dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19DOI: 10.1101/2024.08.15.24312034
Hu Jingyi, Xiu-Li Xiao, Yi Lu, Jian-Yong Su, Yan Zhang, Ting Shang, Chun-Hua Zhang, Lian Guo, Jian-Chao Wang
Objective: The aim of this study was to investigate the prevalence of and potential risk factors associated with skin lesions resulting from the use of medical disinfectants and personal protective equipment (PPE) among epidemic prevention workers (including healthcare professionals, temporary sampling site workers, community members and volunteers) during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic lockdown period in China. Methods: We conducted a survey to investigate the prevalence and factors associated with skin lesions during SARS-CoV-2 pandemic lockdown period among epidemic prevention workers in Gaojing town of Baoshan distract, Shanghai, China. Results: A total of 1033 questionnaires were reviewed, with 995 deemed valid. Among the 995 respondents, 209 (21.01%) reported comorbidities, while 786 (78.99%) were considered as controls. Autoimmune diseases, family history of dermatitis, cardiovascular diseases (CVDs), palmar and plantar hyperhidrosis, allergic diseases and the total time spent on skin cleansing and antisepsis procedures were identified as independent risk factors for these skin lesions. Conclusion: During the SARS-CoV-2 pandemic lockdown period, skin lesions among epidemic prevention workers was prevalent, which was primarily attributed to the use of medical disinfectants and PPE. These skin lesions frequently manifested as a combination of various subtypes across different areas of the body. Several individual factors, along with the total time spent on skin cleansing and skin antisepsis procedures, were identified as significant risk factors for the development of these skin lesions.
{"title":"Epidemiological Study and Analysis of Factors Related to Skin Lesions Caused by Medical Disinfectants, and Personal Protective Equipment among Epidemic-Prevention Workers During the SARS-CoV-2 Pandemic Lockdown Period","authors":"Hu Jingyi, Xiu-Li Xiao, Yi Lu, Jian-Yong Su, Yan Zhang, Ting Shang, Chun-Hua Zhang, Lian Guo, Jian-Chao Wang","doi":"10.1101/2024.08.15.24312034","DOIUrl":"https://doi.org/10.1101/2024.08.15.24312034","url":null,"abstract":"Objective: The aim of this study was to investigate the prevalence of and potential risk factors associated with skin lesions resulting from the use of medical disinfectants and personal protective equipment (PPE) among epidemic prevention workers (including healthcare professionals, temporary sampling site workers, community members and volunteers) during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic lockdown period in China. Methods: We conducted a survey to investigate the prevalence and factors associated with skin lesions during SARS-CoV-2 pandemic lockdown period among epidemic prevention workers in Gaojing town of Baoshan distract, Shanghai, China. Results: A total of 1033 questionnaires were reviewed, with 995 deemed valid. Among the 995 respondents, 209 (21.01%) reported comorbidities, while 786 (78.99%) were considered as controls. Autoimmune diseases, family history of dermatitis, cardiovascular diseases (CVDs), palmar and plantar hyperhidrosis, allergic diseases and the total time spent on skin cleansing and antisepsis procedures were identified as independent risk factors for these skin lesions. Conclusion: During the SARS-CoV-2 pandemic lockdown period, skin lesions among epidemic prevention workers was prevalent, which was primarily attributed to the use of medical disinfectants and PPE. These skin lesions frequently manifested as a combination of various subtypes across different areas of the body. Several individual factors, along with the total time spent on skin cleansing and skin antisepsis procedures, were identified as significant risk factors for the development of these skin lesions.","PeriodicalId":501385,"journal":{"name":"medRxiv - Dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1101/2024.07.30.24311221
Elliot Flint, Nabeel Ahmad, Kevin Rowland, Charles Hildebolt, David M Raskin
Atopic Dermatitis (AD) is a chronic skin disease that commonly appears during childhood but can present at any age. There are many reports showing that probiotics relieve AD symptoms in children. This systematic review and meta-analysis sought to determine the efficacy of topical probiotic treatment for AD in adult populations. A database search was conducted of peer-reviewed, double-blind clinical trials, and studies underwent a systematic exclusion and inclusion process, yielding four that met the criteria. Disease severity, as measured by a standardized scoring tool (SCORAD), was collected, and compared to placebo at two-week and four-week time points. All studies showed improvement in SCORAD in the treatment groups compared to baseline at all time points. Two showed significant decreases in SCORAD after two weeks of treatment, and three studies showed long-lasting improvement after four weeks of treatment. Interestingly, while each study showed a reduction in severity of AD at the two- and four-week time points, a pooled meta-analysis did not show a statistically significant difference between treatment and control at four weeks of treatment. Clinically, there may be benefits to topical probiotic usage as evidenced by the individual studies, more studies need to be performed including adults to show statistical significance.
{"title":"Topical Probiotics Decrease the Severity of Atopic Dermatitis. A Systematic Review and Meta-Analysis of Double-Blind, Randomized, Placebo Control Trials","authors":"Elliot Flint, Nabeel Ahmad, Kevin Rowland, Charles Hildebolt, David M Raskin","doi":"10.1101/2024.07.30.24311221","DOIUrl":"https://doi.org/10.1101/2024.07.30.24311221","url":null,"abstract":"Atopic Dermatitis (AD) is a chronic skin disease that commonly appears during childhood but can present at any age. There are many reports showing that probiotics relieve AD symptoms in children. This systematic review and meta-analysis sought to determine the efficacy of topical probiotic treatment for AD in adult populations. A database search was conducted of peer-reviewed, double-blind clinical trials, and studies underwent a systematic exclusion and inclusion process, yielding four that met the criteria. Disease severity, as measured by a standardized scoring tool (SCORAD), was collected, and compared to placebo at two-week and four-week time points. All studies showed improvement in SCORAD in the treatment groups compared to baseline at all time points. Two showed significant decreases in SCORAD after two weeks of treatment, and three studies showed long-lasting improvement after four weeks of treatment. Interestingly, while each study showed a reduction in severity of AD at the two- and four-week time points, a pooled meta-analysis did not show a statistically significant difference between treatment and control at four weeks of treatment. Clinically, there may be benefits to topical probiotic usage as evidenced by the individual studies, more studies need to be performed including adults to show statistical significance.","PeriodicalId":501385,"journal":{"name":"medRxiv - Dermatology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141862736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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